Neofax 2020 (430-791)

5/7/2020 NeoFax® Drug Monograph Summary - MICROMEDEX
423
concentrations and longer wait times will shorten the time to steady-state [4][5][6]. Other
studies have examined preconditioning and/or priming volumes; running a certain volume of
insulin infusion through the tubing prior to initiation [4][6]. One study demonstrated that 20
mL of priming volume was sufficient to minimize adsorption losses for a 1 unit/mL insulin
infusion [7]. Results show that pre-flushing IV administration sets leads to greater and more
predictable insulin delivery over time [4][8][6] and that the combination of preconditioning
and flushing offers the best combination to reduce insulin adsorption [4][6].
MEDICATION SAFETY
Contraindications/Precautions
Contraindications
During episode of hypoglycemia [12][10]
Hypersensitivity to human regular insulin or any of its components [12][10]
Precautions
Administration: Do not administer 500 units/mL concentration IV, IM, or via insulin pump;
do not dilute or mix with any other insulin products or solutions [10]
Administration: Pen devices and syringes are for single patient use only and never to be
shared, even if the needle is changed, due to increased risk for transmission of bloodborne
pathogens [12][10]
Concomitant use: Concomitant peroxisome proliferator-activated receptor (PPAR)-gamma
agonist therapy may cause dose-related fluid retention, potentially leading to new or
worsening heart failure; monitoring recommended and dose reduction or discontinuation of
PPAR-gamma agonist therapy may be required if heart failure develops [12][10]
Endocrine and metabolic: Hyperglycemia or hypoglycemia may occur with changes in
insulin regimen; increased glucose monitoring recommended [12][10]
Endocrine and metabolic: Severe hypoglycemia may occur 18 to 24 hours after
administration with 500 units/mL [10]
Endocrine and metabolic: Symptomatic hypoglycemia may be difficult to recognize in
patients with longstanding diabetes, patients with nerve disease, patients using medications
that block the sympathetic nervous system (eg, beta blocker) or patients who experience
recurrent hypoglycemia; increased glucose monitoring recommended [12][10]
Endocrine and metabolic: Increased risk for hypoglycemia with injection site changes,
changes in meal patters, changes in level of physical activity, changes to coadministered
medication, and patients with renal or hepatic impairment; increased glucose monitoring
recommended [13][12][10]
Endocrine and metabolic: Increased risk of hyperglycemia with repeated injections into
areas of lipodystrophy or localized cutaneous amyloidosis [13]
Endocrine and metabolic: Hypokalemia may occur; monitoring recommended in patients
at risk for hypokalemia (eg, patients using potassium-lowering medications, patients taking
medications sensitive to serum potassium) [12][10]
Hepatic: Patients with hepatic impairment may require more frequent dose adjustments
[12][10]
Immunologic: Severe, life-threatening, generalized allergy, including anaphylaxis, have
been reported; discontinue if reactions occur [12][10]
Medication errors: Hyperglycemia, hypoglycemia, and death have been reported due to
medication error with 500 units/mL; ensure correct insulin is being used [10]
Renal: Patients with renal impairment may require more frequent dose adjustments [12]
https://www.micromedexsolutions.com/micromedex2/librarian/CS/522936/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 2/5
424
[10]
Adverse Effects
May rapidly induce hypoglycemia. Insulin resistance may develop, causing a larger dose
requirement. Euglycemic hyperinsulinemia due to exogenous insulin administration may
cause metabolic acidosis.
The most recent randomized controlled trial (Beardsall) and systematic review (Raney)
concluded that routine use of insulin in VLBW infants to promote growth is not warranted.
Solution Compatibility
D5W, and D10W, and NS.
Terminal Injection Site Compatibility
Insulin 0.2 unit/mL: Aztreonam (20 mg/mL), magnesium sulfate (40 mg/mL), meperidine
hydrochloride (10 mg/mL), meropenem (1 mg/mL), ritodrine hydrochloride (0.3 mg/mL),
terbutaline sulfate (20 mcg/mL), ticarcillin disodium (30 mg/mL), ticarcillin
disodium/clavulanate potassium (31 mg/mL), vancomycin hydrochloride (4 mg/mL)
Insulin 1 unit/mL: Acyclovir sodium (7 mg/mL), amphotericin B lipid complex (abelcet; 1
mg/mL), anidulafungin (0.5 mg/mL), argatroban (1 mg/mL), atenolol (0.5 mg/mL),
bivalirudin (5 mg/mL), caspofungin acetate (0.5 mg/mL), ceftaroline fosamil (2.22 mg/mL),
dexmedetomidine hydrochloride (4 mcg/mL), doripenem (5 mg/mL), doxapram hydrochloride
(2 mg/mL), ertapenem sodium (20 mg/mL), esomeprazole sodium (0.32 mg/mL),
fenoldopam mesylate (80 mcg/mL), foscarnet sodium (24 mg/mL), fosphenytoin sodium (20
mg/mL), gatifloxacin (2 mg/mL), granisetron hydrochloride (50 mcg/mL), hetastarch 6% (1
unit/mL), hydromorphone hydrochloride (0.5 mg/mL), ibuprofen lysine (10 mg/mL),
leucovorin calcium (2 mg/mL), linezolid (2 mg/mL), lorazepam (0.5 mg/mL), magnesium
sulfate (8 mg/mL), methadone hydrochloride (0.2 mg/mL), methotrexate sodium (15
mg/mL), metronidazole (5 mg/mL), milrinone lactate (0.4 mg/mL), moxifloxacin
hydrochloride (1.6 mg/mL), mycophenolate mofetil hydrochloride (6 mg/mL), nitroglycerin
(0.2 mg/mL), nitroprusside sodium (0.2 mg/mL, 1.2 mg/mL), octreotide acetate (5 mcg/mL),
oritavancin (0.8 mg/mL), palonosetron hydrochloride (50 mcg/mL), pamidronate disodium
(0.3 mg/mL), pancuronium bromide (0.1 mg/mL), pentobarbital sodium (2 mg/mL),
potassium acetate (0.2 mEq/mL), propofol (10 mg/mL), remifentanil hydrochloride (0.12
mg/mL), sodium bicarbonate (1 mEq/mL), sufentanil citrate (5 mcg/mL), tacrolimus (20
mcg/mL), tigecycline (1 mg/mL), vecuronium bromide (1 mg/mL), voriconazole (4 mg/mL),
zoledronic acid (40 mcg/mL)
Insulin 4 units/mL: Clarithromycin (4 mg/mL)
Insulin 40 units/mL: Potassium chloride (40 mEq/L), vitamin B complex with C (2 mL/L)
Insulin 50 units/mL: Alfentanil hydrochloride (0.25 mg/mL), aminophylline (12.5 mg/mL),
ascorbic acid injection (250 mg/mL), atropine sulfate (0.5 mg/mL), azathioprine sodium
(13.33 mg/mL), aztreonam (80 mg/mL), benztropine mesylate (0.5 mg/mL), bretylium
tosylate (40 mg/mL), bumetanide (0.125 mg/mL), buprenorphine hydrochloride (0.15
425
mg/mL), calcium chloride (50 mg/mL), calcium gluconate (50 mg/mL), cefamandole nafate
(333 mg/mL), cefazolin sodium (220 mg/mL), cefotaxime (285 mg/mL), ceftazidime (400
mg/mL), ceftizoxime (400 mg/mL), ceftriaxone sodium (165 mg/mL), cefuroxime (125
mg/mL), chloramphenicol sodium succinate (333 mg/mL), cimetidine hydrochloride (24
mg/mL), clindamycin phosphate (48 mg/mL), cyanocobalamin (0.5 mg/mL), dexamethasone
sodium phosphate (12 mg/mL), doxycycline hyclate (4 mg/mL), enalaprilat (0.625 mg/mL),
ephedrine sulfate (12.5 mg/mL), epoetin alfa (5000 units/mL), erythromycin lactobionate (20
mg/mL), esmolol hydrochloride (40 mg/mL), fentanyl citrate (25 mcg/mL), fluconazole (2
mg/mL), folic acid (0.4 mg/mL), ganciclovir sodium (40 mg/mL), hydrocortisone sodium
succinate (62.5 mg/mL), hydroxyethylstarch 130/0.4 6%, imipenem-cilastin sodium (5
mg/mL), indomethacin sodium trihydrate (1 mg/mL), ketorolac tromethamine (15 mg/mL),
lactated ringer's injection, lidocaine hydrochloride (10 mg/mL), mannitol (150 mg/mL),
methyldopate hydrochloride (25 mg/mL), methylprednisolone sodium succinate (125
mg/mL), metoclopramide hydrochloride (2.5 mg/mL), metoprolol tartrate (0.5 mg/mL),
nalbuphine hydrochloride (10 mg/mL), netilmicin sulfate (50 mg/mL), oxacillin sodium (160
mg/mL), papaverine hydrochloride (15 mg/mL), penicillin G potassium (500,000 units/mL),
penicillin g sodium (500,000 units/mL), pentazocine lactate (15 mg/mL), phenobarbital
sodium (65 mg/mL), phytonadione (5 mg/mL), piperacillin sodium (320 mg/mL),
procainamide hydrochloride (250 mg/mL), promethazine hydrochloride (25 mg/mL),
pyridoxine hydrochloride (50 mg/mL), Ringer's injection, streptokinase (80,000 units/mL),
theophylline (4 mg/mL), thiamine (50 mg/mL), urokinase (50,000 units/mL), verapamil
hydrochloride (1.25 mg/mL)
Insulin 100 units/mL: Cefepime hydrochloride (120 mg/mL), naloxone hydrochloride (0.4
mg/mL)
Terminal Injection Site Incompatibility
Butorphanol tartrate, cefoperazone, cefoxitin, ceftobiprole medocaril, chlorpromazine

hydrochloride, dantrolene sodium, diazepam, diazoxide, diphenhydramine hydrochloride,
drotrecogin alfa (activated), glycopyrrolate, hydroxyzine hydrochloride, inamrinone lactate,
isoproterenol hydrochloride, ketamine hydrochloride, labetalol hydrochloride, micafungin
sodium, minocycline hydrochloride, nesiritide, pentamidine isethionate, phentolamine
mesylate, phenylephrine hydrochloride, phenytoin sodium, piperacillin sodium/tazobactam
sodium, polymyxin b sulfate, prochlorperazine edisylate, propranolol hydrochloride,
protamine sulfate, quinidine gluconate, quinupristin/dalfopristin, rocuronium bromide,
sulfamethoxazole/trimethoprim,
Monitoring
Follow blood glucose concentration frequently (every 15 to 30 minutes) after starting insulin
infusion and after changes in infusion rate. Monitor potassium concentrations closely when
treating hyperkalemia.
MECHANISM OF ACTION/PHARMACOKINETICS
426
Pharmacology
Degraded in liver and kidney. Enhances cellular uptake of glucose, conversion of glucose to
glycogen, amino acid uptake by muscle tissue, synthesis of fat, and cellular uptake of
potassium. Inhibits lipolysis and conversion of protein to glucose. Plasma half-life in adults is
9 minutes.
ABOUT
Special Considerations/Preparation
Available: Regular human insulin [rDNA origin] is available as a 100-unit/mL concentration

in 10-mL vials.
Dilution: For subcutaneous administration, dilute with sterile water or NS to a concentration
of 0.5 or 1 unit/mL. For IV administration, make a 10 units/mL dilution with sterile water,
then further dilute in compatible solution to a concentration of 0.05 to 1 unit/mL. Keep
refrigerated.
© Copyright IBM Corporation 2020
427
Ipratropium
NeoFax® Drug Monograph Summary - MICROMEDEX
DOSING/ADMINISTRATION
Dose
Administer every 6 to 8 hours as a metered dose inhaler (MDI) or nebulized solution.

Doses studied in intubated neonates range from 2 puffs (34 mcg) to 4 puffs (68 mcg) via
MDI with spacer device placed in the inspiratory limb of the ventilator circuit, and 75 to 175
mcg via jet nebulizer. Simulated neonatal lung models suggest greater delivery when using a
spacer with the MDI. Use chlorofluorocarbon free preparations when administering to
neonates.
Optimal dose in neonates has yet to be determined due to differences in aerosol drug
delivery techniques, although the therapeutic margin appears to be wide.
Uses
Anticholinergic bronchodilator for primary treatment of chronic obstructive pulmonary

diseases and adjunctive treatment of acute bronchospasm. Ipratropium is not useful in the
treatment of bronchiolitis.
MEDICATION SAFETY
Adverse Effects
Temporary blurring of vision, precipitation of narrow-angle glaucoma, or eye pain may occur
if solution comes into direct contact with the eyes.
Monitoring
Assess degree of bronchospasm.
Pharmacology
https://www.micromedexsolutions.com/micromedex2/librarian/CS/E85547/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/2
428
Ipratropium bromide is a quaternary ammonium derivative of atropine. It produces primarily
large airway bronchodilation by antagonizing the action of acetylcholine at its receptor site. It
is relatively bronchospecific when administered by inhalation because of limited absorption
through lung tissue. Peak effect occurs 1 to 2 hours after administration. Duration of effect is
4 to 6 hours in children. The combination of ipratropium with a beta-agonist produces more
bronchodilation than either drug individually.
ABOUT
Metered-dose inhaler: Atrovent® HFA is available in a pressurized metered-dose aerosol

unit (contains no chlorofluorocarbons (CFC)) providing 200 actuations per each 12.9-g
canister. Each actuation delivers 21 mcg of ipratropium from the valve and 17 mcg from the
mouthpiece.
Solution for inhalation: Supplied in 2.5-mL vials, containing ipratropium bromide 0.02%
(200 mcg/mL) in a sterile, preservative-free, isotonic saline solution that is pH-adjusted to
3.4 with hydrochloric acid. It may be mixed with albuterol or metaproterenol if used within 1
hour. Store at room temperature in foil pouch provided. Protect from light.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/E85547/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 2/2
429
Iron Dextran
Dose
0.4 to 1 mg/kg (400 to 1000 mcg/kg) per day IV continuous infusion .
Uses
Iron supplementation in patients unable to tolerate oral iron, especially those also being
treated with erythropoietin.
Administration
For continuous infusion, iron dextran may be added to peripheral nutrition solutions. The
solution must contain an amino acid final concentration of at least 2% [1].
MEDICATION SAFETY
Adverse Effects
No adverse effects have been observed in patients who have received low doses infused
continuously. Large (50-mg) intramuscular doses administered to infants were associated
with increased risk of infection. Retrospective reviews of adult patients who received larger
doses injected over a few minutes report a 0.7% risk of immediate serious allergic reactions,
and a 5% risk of delayed such as myalgia, arthralgia, phlebitis, and lymphadenopathy.
Black Box Warning
Anaphylactic-type reactions, including fatalities, have followed parenteral administration.

Resuscitation equipment and trained personnel must be readily available during iron dextran
administration. Must perform test dose. Observe for signs/symptoms of anaphylactic-type
reactions. Fatal reactions have occurred following the test dose and have occurred in
situations where the test dose was tolerated. Patients with a history of drug allergy or
multiple drug allergies may be at increased risk of anaphylactic-type reactions.
Monitoring
…/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.PrintLandingPageDocument 1/2
430
Periodic CBC and reticulocyte count. Observe Dex/AA solution for rust-colored precipitates..
Pharmacology
Iron dextran for intravenous use is a complex of ferric hydroxide and low molecular mass
dextran. The dextran serves as a protective lipophilic colloid. Radiolabeled iron dextran
injected into adult subjects localized to the liver and spleen before being incorporated into
RBC hemoglobin. Complete clearance occurred by 3 days. Approximately 40% of the labeled
iron was bound to transferrin within 11 hours. The addition of iron dextran to Dex/AA
solutions inhibits the spontaneous generation of peroxides..
ABOUT
Available as a 50 mg/mL concentration in 2-mL single-dose vials. Store at room temperature.

Iron dextran products are not interchangeable[2].
431
Isoproterenol
Dose
0.05 to 0.5 mcg/kg/minute continuous IV infusion.

Maximum dose 2 mcg/kg per minute.
Dosage often titrated according to heart rate.
Acidosis should be corrected before infusion.
Uses
Increases cardiac output in patients with cardiovascular shock. Pulmonary vasodilator (older
infants).
Administration
Solution Preparation Calculations
Maximum concentration 20 mcg/mL. Concentrations as low as 2 mcg/mL has been used

in adults [1]
To calculate the AMOUNT of drug needed per defined final fluid volume:
Desired final concentration (mg/mL) x defined final fluid volume (mL) = AMOUNT of drug to
add to final infusion solution (mg).
To calculate the VOLUME of drug needed per defined final fluid volume:
*AMOUNT of drug to add (mg) ÷ drug (vial) concentration (mg/mL) = VOLUME of drug to
add (mL)
Example (for Isoproterenol): Mix 50 mL of 10 mcg/mL solution using isoproterenol

concentration of 0.2 mg/mL.
10 mcg/mL = 0.01 mg/mL
0.01 mg/mL x 50 mL = 0.5 mg isoproterenol
*0.5 mg ÷ 0.2 mg/mL = 2.5 mL of isoproterenol
Add 2.5 mL of isoproterenol (0.2 mg/mL) to 47.5 mL of compatible solution (eg, D5W) to
yield 50 mL of infusion solution with a concentration of 10 mcg/mL.
Isoproterenol Titration Chart

Concentration Dose IV Rate
(mcg/mL) (mcg/kg/min) (mL/kg/hour)
5 0.05 0.6
https://www.micromedexsolutions.com/micromedex2/librarian/CS/0DE1F8/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
432
0.1 1.2
0.5 6
1 12
0.05 0.3
0.1 0.6
10
0.5 3
1 6
0.05 0.2
0.1 0.4
15
0.5 2
1 4
0.05 0.15
0.1 0.3
20
0.5 1.5
1 3
MEDICATION SAFETY
Adverse Effects
Cardiac arrhythmias. Tachycardia severe enough to cause CHF. Decreases venous return to
heart. Systemic vasodilation. May cause hypoxemia by increasing intrapulmonary shunt.
Hypoglycemia.
D5W, D10W, and NS.
Amiodarone, caffeine citrate, calcium chloride, calcium gluceptate, cimetidine, dobutamine,

famotidine, heparin, hydrocortisone succinate, milrinone, netilmicin, nitroprusside,
pancuronium bromide, potassium chloride, propofol, ranitidine, remifentanil, and vecuronium.
Furosemide and sodium bicarbonate.
Monitoring
433
Continuous vital signs, intra-arterial blood pressure, CVP monitoring preferable. Periodic
blood glucose reagent strips.
Pharmacology
β-receptor stimulant, sympathomimetic. Increases cardiac output by 1) increasing rate

(major) and 2) increasing strength of contractions (minor). Insulin secretion is stimulated.
Afterload reduction via β2 effects on arterioles.
ABOUT
Supplied as 0.2 mg/mL solution in 1-mL and 5-mL ampuls.
434
LamiVUDine
Dose
Screen for Hepatitis B virus prior to initiating therapy [1].

HIV Infection, Treatment and Perinatal Prophylaxis:
32 weeks' gestation or more:
Birth to 4 weeks' postnatal age: 2 mg/kg/dose orally every 12 hours [1].
4 to 6 weeks' postnatal age: 4 mg/kg/dose orally every 12 hours [1].
Dose Adjustments
Renal Impairment: Although there are no dosing recommendations available for neonates
or pediatric patients with renal impairment, a reduction in the dose and/or an increase in the
dosing interval should be considered [2].
Uses
Antiretroviral Management in the Newborn[1]
Risk of HIV
Description Antiretroviral (ARV) Management †
in Newborn
•Mother had consistent viral
suppression near delivery with
Low risk of
standard combination ARV therapy Zidovudine for 4 weeks
transmission
during pregnancy and was adherent
to the regimen
•Mother has not received antepartum
or intrapartum ARV therapy.
•Mother has received only •Dual ARV prophylaxis with 6 weeks zidovudine
intrapartum ARV therapy and 3 doses of nevirapine (prophylaxis dosage,
•Mother has received antepartum with doses within 48 hours of birth, 48 hours
Higher risk
and intrapartum ARV drugs but does later, and 96 hours after the second dose) OR
of
not have viral suppression near •Empiric therapy: zidovudine, lamiVUDine, and
transmission
delivery, particularly with vaginal treatment doses of nevirapine †† OR
delivery • Empiric therapy: zidovudine, lamiVUDine, and
•Mother has acute or primary HIV raltegravir ††
infection during pregnancy or
breastfeeding #
•Mother with unknown HIV status •ARV management is the same as those with
Presumed who test positive at delivery or higher risk of transmission (see above).
exposure postpartum or whose newborn has •Discontinue immediately if supplemental
positive HIV antibody test. testing confirms mother does not have HIV.
•3-drug regimen (zidovudine, lamiVUDine, and
•Confirmed positive newborn HIV nevirapine) at treatment dosage OR
Confirmed
virologic test/nucleic acid test. •3-drug regimen (zidovudine, lamiVUDine and
raltegravir)
KEY
435
† = Initiate ARV drugs as close to the time of birth as possible, preferably within 6 to 12 hours of
delivery.
†† = Optimal duration is unknown, zidovudine should always be continued for 6 weeks. When the
nucleic acid test at birth is negative, some experts may discontinue nevirapine, raltegravir, and/or
lamiVUDine while others may continue empiric therapy for 6 weeks.
# = Due to a higher risk for in utero transmission to infants whose mothers had acute HIV during
pregnancy, most experts would administer empiric HIV therapy. Discontinue breastfeeding if acute
or primary HIV infection occurs during breastfeeding.
AIDSinfo, April 2019
Prevention of maternal-fetal HIV transmission: In a phase III randomized trial

(n=1684), the combination of 6 weeks of zidovudine plus 3 doses of nevirapine or the
combination of 6 weeks of zidovudine plus nelfinavir and lamiVUDine for 2 weeks was
associated with a lower intrapartum transmission rate when compared with zidovudine alone
in infants born to women who received no antenatal antiretroviral therapy (2.2% versus
2.5% versus 4.9%, respectively). The zidovudine/nelfinavir/lamiVUDine regimen was
associated with increased toxicity (eg, neutropenia) [3].
Pediatric FDA Approved Indications

Epivir®
Treatment of HIV-1 infection in combination with other antiretroviral agents in children 3
months of age and older [2].
Administration
Can be given without regard to meals [2].
MEDICATION SAFETY
Dual-NRTI therapy with emtricitabine and lamiVUDine is NOT recommended in children due
to similar resistance patterns and no additive benefit [1] .
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, has
been reported, with increased risk in women and obese patients. Interrupt therapy if lactic
acidosis or pronounced hepatotoxicity, which may include hepatomegaly and steatosis even
in the absences of marked transaminase elevations, is suspected [4]
Exacerbation of hepatitis has occurred after discontinuation of lamivudine. Most cases
were self-limited, but fatalities have been reported. Monitoring for several months after
treatment discontinuation is recommended [5].
Emergence of lamivudine-resistant HBV has occurred in HIV-1 infected subjects on
lamivudine in the presence of concurrent infection with hepatitis B virus [6].
Pancreatitis may occur. Exercise caution in patients with a history of antiretroviral
nucleoside exposure, a history of pancreatitis, of other risk factors. Discontinue treatment if
signs and symptoms of pancreatitis occur [5].
Immune reconstitution syndrome has been reported with combination antiretroviral
therapy and may require further evaluation or treatment [5].
436
Autoimmune disorders (eg, Graves' disease, polymyositis, Guillain-Barre syndrome) have
been reported in the setting of immune reconstitution. May occur many months after
initiation of treatment [5]
Compared with tablets, the oral solution resulted in lower rates of virologic suppression,
lower plasma lamivudine exposure, and increased development of viral resistance in pediatric
patients [6].
Adverse Effects
Adverse effects reported in neonates were increased liver function tests, anemia, diarrhea,
electrolyte disturbances, hypoglycemia, jaundice and hepatomegaly, rash, respiratory
infections, sepsis, gastroenteritis (with associated convulsions), and transient renal
insufficiency associated with dehydration. Deaths (1 from gastroenteritis with acidosis and
convulsions, 1 from traumatic injury, and 1 from unknown causes) were reported in 3
neonates. [2].
Black Box Warning
Epivir®[4]
Exacerbations of Hepatitis B
Severe acute exacerbations of hepatitis B have been reported in patients who are co-
infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and
have discontinued lamivudine. Hepatic function should be monitored closely with both
clinical and laboratory follow-up for at least several months in patients who discontinue
lamivudine and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-
hepatitis B therapy may be warranted.
Important Differences Among Lamivudine-Containing Products
Epivir® tablets and oral solution (used to treat HIV-1 infection) contain a higher dose of
the active ingredient (lamivudine) than Epivir-HBV® tablets and oral solution (used to
treat chronic hepatitis B virus infection). Patients with HIV-1 infection should receive
only dosage forms appropriate for treatment of HIV-1.
Monitoring
[1]
Antiretroviral Monitoring in Children (adjust schedule based on the specific antiretroviral regimen)
1 to 2 2 to 4
weeks weeks Every 3 to 4 Only required every 6 to 12 Therapy
after after months months Switch
Baseline initiation initiation
†
If clinical, immunologic, or virologic deterioration is suspected, perform more
frequent CD4 cell count and plasma viral load monitoring. If toxicity noted,
perform testing more frequently until toxicity resolved
Adverse X X X X X
437
Effects ††
Adherence
Evaluation X X X X X
††
CBC with
differential X X X X
¶
Chemistries
X X X X
‡¶
Lipid Panel X X ‡‡
Random
Plasma X X
Glucose
Urinalysis X X♦
CD4 count
X X¶ X
†† ♦♦
HIV RNA
X X X X
††
Resistance
X ¶¶ X
Testing
Hepatitis B
screening X X
≈
KEY: CBC = complete blood count
† Baseline may not be necessary if pre-therapy monitoring was performed within 30 to 90 days.
† † Monitor for adherence, effectiveness (CD4 cell count and plasma viral load [HIV RNA]), and
toxicities every 3 to 4 months.
‡ Chemistries include electrolytes, creatinine, glucose, and hepatic transaminases.
‡‡ If lipids have been abnormal in the past, more frequent monitoring might be needed.
♦ Consider more frequent urinalysis in patients taking tenofovir disoproxil fumarate.
♦ ♦ In all children, absolute CD4 cell count is recommended; CD4 percentage is an alternative for
children younger than 5 years.
¶ CD4 cell count, CBC, and chemistries can be monitored less frequently (every 6 to 12 months) in
children and youth who are adherent to therapy and have CD4 cell count values well above the
threshold for opportunistic infection risk, have sustained viral suppression, and have stable clinical
status for more than 2 to 3 years.
¶¶ Obtain virus resistance testing even if antiretroviral therapy is not immediately started.
≈ Only if individual previously demonstrated no immunity to hepatitis B and when initiating a
regimen that contains agents with activity against hepatitis B (ie, lamivudine, emtricitabine,
tenofovir alafenamide, or tenofovir disoproxil fumarate.
Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, April, 2019; AIDSinfo
Monitor for signs/symptoms of pancreatitis (eg, persistent abdominal pain, fever, nausea,
vomiting, or diarrhea) [2].
Consider more frequent monitoring of viral load when treating with the solution of lamivudine
[4].
Pharmacology
438
lamiVUDine (3TC) is a synthetic nucleoside analog that inhibits HIV and HBV replication by
interfering with viral reverse transcriptase. It is intracellularly converted in several steps to
the active compound, and then renally excreted. Poor CNS penetration with a percent CSF to
serum drug concentration of approximately 12%. The oral solution is well-absorbed, with
66% bioavailability in children. Peak reached in 0.5 to 1.5 hours. Primarily eliminated as
unchanged drug in the urine. The serum half-life in children is approximately 2.2 +/- 2 hours.
Clearance reduced in renal impairment; dose reduction recommended. Viral resistance
develops rapidly to monotherapy with lamiVUDine (3TC) [2][7].
In 36 infants up to 1 week of age administered lamiVUDine and zidovudine, lamiVUDine
clearance was substantially reduced in 1-week-old neonates compared with children older
than 3 months of age [2].
ABOUT
Available as an oral solution in concentrations of 5 mg/mL (Epivir-HBV®) and 10 mg/mL

(Epivir®). Oral tablets available in 100-mg (Epivir-HBV®), 150-mg (Epivir®), and 300-mg
(Epivir®) strengths. Store at room temperature.[2][8].
439
Lansoprazole
Dose
0.73 to 1.66 mg/kg/dose orally once daily.
Uses
Crying and irritability: In otherwise healthy term infants, histamine2 receptor antagonists
or proton pump inhibitors should not be used for the treatment of crying and distress [1]. No
improvement in crying and irritability was provided by proton pump inhibitors in infants in a
systematic review of 5 randomized clinical trials (n=430) [2].
Gastroesophageal Reflux (GER): The risks associated with acid reducing agents
outweighs the benefits in preterm infants for GER. Acid blocking agents should not be used
and if used in preterm infants, use sparingly [3]. In otherwise healthy term infants,
histamine2 receptor antagonists or proton pump inhibitors should not be used for the
treatment of visible regurgitation [1].
Gastroesophageal Reflux Disease (GERD): Proton pump inhibitors (PPIs) are the first-
line agents for erosive esophagitis in infants and children with GERD. Histamine2 receptor
antagonists are the second-line agent if PPIs are not available or are contraindicated. A
duration of treatment for 4 to 8 weeks for GERD symptoms is recommended. Regularly
reassess the need for long-term acid suppression. If no response after 4 to 8 weeks, then re-
evaluate for other causes of symptoms. H2RAs and PPIs are not recommended for
extraesophageal symptoms (e.g. cough, wheezing, asthma), unless GERD symptoms are
present and/or GERD has been diagnosed [1].
A trial use of PPIs as a diagnostic test for GERD is not recommended in infants or in patients
presenting with extraesophageal symptoms. However, in children with typical GERD
symptoms, a trial of 4 to 8 weeks with a PPI may be used as a diagnostic test [1].
Administration
The contents of a capsule can be mixed in 40 mL of apple juice and administered by NG

tube. Do not use other liquids. The NG tube should be flushed with additional apple juice
after administration. Data for successfully supplying patient-specific, partial doses of
lansoprazole through pediatric/neonatal feeding tubes are lacking. In one study attempting
to provide a partial dose (orally disintegrating tablet formulation) through a feeding tube, a
7.5 mg dose was administered successfully through an 8 French pediatric feeding tube;
however, the same dose partially clogged a 6 French pediatric feeding tube (was able to
clear with NS flush) and completely clogged a 5 French pediatric feeding tube.
There have been reports to the FDA of Teva's lansoprazole delayed-release orally
440
disintegrating tablets causing clogged and blocked oral syringes, and gastric and jejunostomy
feeding tubes requiring patients to seek emergency medical assistance to have feeding tubes
unclogged or removed and replaced. Tablets may not disintegrate entirely when water is
added to form a suspension, and/or the tablets may disintegrate but later form clumps which
can adhere to the inside walls of the tubes. The FDA recommends that the Teva brand of
delayed-release orally disintegrating lansoprazole tablets not be dispensed to patients with
feeding tubes.
MEDICATION SAFETY
CONTRAINDICATIONS
Contraindicated with rilpivirine-containing products [4][5].
PRECAUTIONS
Increased serum chromogranin A (CgA) levels may occur and lead to false positive results in
diagnostic investigations for neuroendocrine tumors; therapy interruption may be necessary
prior to laboratory assessments [4][5].
Use caution in patients with phenylketonuria, as oral disintegrating tablets contain
phenylalanine [4][5].
New onset or worsening cutaneous lupus erythematosus (CLE) and systemic lupus
erythematosus (SLE) have been reported with proton pump inhibitor use. Avoid using for
longer than medically indicated and discontinue use if signs or symptoms of CLE or SLE
develop [6][7]
Hypomagnesemia has been reported with prolonged administration (in most cases, greater
than 1 year) of proton pump inhibitors. Concomitant use of drugs that cause
hypomagnesemia may increase the risk. Monitoring is recommended during therapy. In some
cases, hypomagnesemia was not reversed with magnesium supplementation and
discontinuation of the proton pump inhibitor was necessary.
Acute interstitial nephritis may occur (typically due to idiopathic hypersensitivity
reaction); discontinue if it occurs [8][9].
Cyanocobalamin (vitamin B12) deficiency may occur with long term use [8][9].
Infection: Increased risk of infections (necrotizing enterocolitis, pneumonia, upper
respiratory tract infections, sepsis, urinary tract infections, and Clostridium difficile
infections)
in infants and children on H2 blockers or PPIs demonstrated in case-control studies [1][10].
Respiratory: PPIs, when used for oropharyngeal dysphagia (off-label use), may be
associated with an increased risk of hospitalization due to aspiration and isolated laryngeal
penetration; demonstrated in a retrospective cohort (n=293 children 2 years or younger)
[11].
Adverse Effects
Hypergastrinemia and mild transaminase elevations are the only adverse effects reported in
children who received lansoprazole for extended periods of time. Available data are limited to
small studies of infants and children.
441
In a retrospective, single-center, observational, case-control study of 136 children (1 year or
older) having protracted diarrhea and stool analysis for Clostridium difficile
, the use of PPI
therapy was significantly higher in the patients with C difficile
-associated diarrhea compared
to the control group (22% vs 6%; odds ratio of 4.5 (95% CI, 1.4 to 14.4; p=0.006)) [12].
Monitoring
Observe for symptomatic improvement within 3 days. Consider intraesophageal pH

monitoring to assess for efficacy (pH greater than 4.0). Measure AST and ALT if duration of
therapy is greater than 8 weeks. Hypomagnesemia has been reported with prolonged
administration (in most cases, greater than 1 year). Monitor magnesium levels prior to
initiation of therapy and periodically during therapy in patients expected to be on long-term
therapy or patients receiving concomitant drugs such as digoxin or those that may cause
hypomagnesemia.
Pharmacology
Lansoprazole inhibits gastric acid secretion by inhibition of hydrogen-potassium ATPase, the

enzyme responsible for the final step in the secretion of hydrochloric acid by the gastric
parietal cell ("proton pump"). Extensively metabolized in the liver by CYP 2C19 and 3A4.
Onset of action is within one hour of administration, maximal effect is at approximately 1.5
hours. Average elimination half-life is 1.5 hours. Inhibition of acid secretion is about 50% of
maximum at 24 hours and the duration of action is approximately 72 hours. The absorption
of weakly acidic drugs (eg, digoxin, furosemide) is enhanced. The absorption of weakly basic
drugs (eg, ketoconazole) is inhibited.
ABOUT
Prevacid® is supplied as a delayed-release capsule and a delayed-release orally

disintegrating tablet (ODT) containing either 15 mg or 30 mg lansoprazole for oral
administration [13][14]. Lansoprazole is also supplied as a suspension through a
compounding kit made by Cutis Pharma. The First ® compounding kit is available in a
concentration of 3 mg/mL in the following sizes: 90 mL, 150 mL, and 300 mL. The kits
contain all necessary ingredients and tools to make the suspension. The suspension is added
to the lansoprazole powder in two additions; shaking well after each addition. The
suspension is stable for 30 days when refrigerated (2 to 8 degrees C/ 36 to 46 degrees F)
and is strawberry flavored [15].
Extemporaneous Preparation
Lansoprazole 3 mg/mL oral suspension was prepared by mixing the contents of ten 30-mg
442
lansoprazole capsules with 100 mL of 8.4% sodium bicarbonate solution for 30 minutes. It
was stored in amber-colored, plastic oral syringes. Stability was maintained for up to 7 days
when refrigerated (3 to 4 degrees C) and up to 48 hours when stored at room temperature
(20 to 22 degrees C). Integrity of the suspension was compromised after these storage times
[16].
443
LevETIRAcetam
Dose
Seizure
Loading Dose: In a retrospective study, neonates received total loading doses of 20 to 150
mg/kg/day IV with doses typically divided into multiple smaller doses administered within a
24-hour period [1].
Maintenance Dose: In retrospective studies that included term and preterm neonates,
maintenance doses were 41.7 mg/kg/day [2] to 65 mg/kg/day IV [1]; upper range doses
were 100 mg/kg/day [1] to 106.2 mg/kg/day [2]. Doses were typically administered every 12
hours [1]. When the route was switched from IV to oral, plasma levETIRAcetam
concentrations remained within the same range [3]. The total daily IV dosage is equivalent to
the total daily oral dosage in patients 1 month or older [4].
Dosage Adjustment
Renal Impairment: There are no recommendations for neonates; however, levETIRAcetam
is primarily eliminated renally [4].
Uses
Seizures: Randomized controlled trials have not been performed for neonatal seizures
treated with levETIRAcetam. A systematic review of 5 observational studies (N=102 preterm
and term neonates) demonstrated complete seizure or near-complete seizure cessation in
63% to 77% of patients with levETIRAcetam as a first- or second-line agent [8]. Seizure
control was achieved in 47% of neonates treated with levETIRAcetam as a first-line agent in
a retrospective chart review (n=36). Fosphenytoin or PHENobarbital was administered to 18
out of the 19 neonates who continued to have seizures. In total, 83% achieved seizure
control with levETIRAcetam monotherapy or levETIRAcetam plus fosphenytoin or
PHENobarbital. At least 1 dose of LORazepam was administered prior to levETIRAcetam in
28% of neonates. The mean levETIRAcetam dosages were 49.8 mg/kg IV loading dose
followed by an initial maintenance dose of 24.8 mg/kg/dose IV every 12 hours. The known
seizure etiologies were HIE (31%), infection (14%), and other (24%; intracranial
hemorrhage, cerebral infarction, neonatal abstinence syndrome, and congenital
malformations) [9].

Tablets, Solution
•Adjunctive therapy in the treatment of partial onset seizures in children 1 month or older
with epilepsy for Keppra [10] or 4 years or older weighing more than 20 kg for Spritam [11].
•Adjunctive therapy in the treatment of myoclonic seizures in children 12 years and older
with juvenile myoclonic epilepsy [11][10].
•Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in children 6
years and older with idiopathic generalized epilepsy [11][10].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/0EFC45/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
444
Extended-Release Tablets
•Adjunctive therapy in the treatment of partial onset seizures in children 12 years or older
with epilepsy [12][13].
Intravenous (as an alternative when oral administration is not feasible)

•Adjunctive therapy in the treatment of partial onset seizures in children 1 month or older
with epilepsy [4].
•Adjunctive therapy in the treatment of myoclonic seizures in children 12 years or older with
juvenile myoclonic epilepsy [4].
•Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in children 6
years or older with idiopathic generalized epilepsy [4].
Administration
Intravenous: Dilute to a concentration of 5 to 15 mg/mL and infuse over 15 minutes [5]. A

standard concentration was 5 mg/mL or 15 mg/mL for intermittent IV administration [6]
Oral: May be given without regards to feedings [7].
MEDICATION SAFETY
Precautions
Cardiovascular: Increased risk for increased diastolic blood pressure has been reported in
pediatric patients 1 month to younger than 4 years [4].
Dermatologic: Serious dermatologic reactions, such as Stevens-Johnson syndrome and
toxic epidermal necrolysis, have been reported; median onset was 14 to 17 days, but other
reports were at least 4 months after initiation. Immediate discontinuation and alternative
therapy recommended if these reactions occur [4]
Discontinuation: Withdraw gradually due to risk of increased seizure frequency and status
epilepticus [14][15][16][12]; serious adverse reactions may prompt consideration for rapid
discontinuation [14][15][16]
Hematologic: Hematologic abnormalities, including decreased WBC, neutrophil, and RBC
counts, decreases in hemoglobin and hematocrit, and increased eosinophil count ;
Agranulocytosis, pancytopenia, and thrombocytopenia have also been reported [4].
Immunologic: Anaphylaxis or angioedema may occur after the first dose or at any time
during treatment; discontinuation is required [4].
Neurologic: Somnolence, fatigue, and asthenia have been reported; somnolence and
asthenia typically occurred within first 4 weeks of treatment; monitoring recommended [12]
Renal: Dosage adjustments are recommended in adult patients with renal impairment [4]
Adverse Effects
Immunologic: An anaphylactic reaction (erythematous rash, urticaria, hypotension)

developed within seconds of the first dose of IV levETIRAcetam in a newborn. He was
445
managed with epinephrine IM and cardiopulmonary resuscitation and the blood pressure
returned to normal. The rash resolved approximate 24 hours later [17]
Neurologic:
After a 2 year follow-up, 280 infants who started antiepileptic agents as neonates
experienced worse neurodevelopmental outcomes (cognitive and motor) with increased
PHENobarbital exposure compared with levETIRAcetam in a retrospective study [18].
Psychiatric:
Behavioral disorders (typically aggression, hostility, and nervousness) were 2-fold more likely
in levETIRAcetam-treated compared with placebo-treated children (1 month or older) with
epilepsy in 3 randomized studies. However, behavioral deteriorations and improvements were
not consistently demonstrated in 10 observational studies [19].
NS, LR, and D5W.
Diazepam, LORazepam, and valproate sodium.
Monitoring
In one small observational study (n=38) levETIRAcetam concentrations were 12.5 to 55

mcg/mL in neonates [3]; however, there is no correlation between plasma concentration and
efficacy.
Pharmacology
Mechanism of action: The exact mechanism of action is unknown [4].
Concentrations
Tmax: 18.2+/-5.9 mcg/mL (1 hour after 20 mg/kg IV) and 33+/-9.8 mcg/mL (1 hours after
40 mg/kg IV) in full-term newborns [20].
Trough: 1.4 mcg/mL (before 5 mg/kg IV doses) and 2 mcg/mL (before 10 mg/kg IV doses)
in full-term newborns [20].
Distribution
Protein Binding: less than 10% [4].
Vd: 0.98 L/kg (0.81 to 1.24 L/kg) in full-term newborns [20]
446
Metabolism: LevETIRAcetam and its major metabolite are neither inhibitors of, nor high
affinity substrates for, human liver cytochrome P450 isoforms, epoxide hydrolase or UDP-
glucuronidation enzymes [4].
Drug Interactions: Levetiracetam had no effect on plasma concentrations of
carbamazepine, valproate, topiramate, or lamotrigine [4].
Excretion
Clearance: 0.65 mL/min/kg (day 1) and 1.33 mL/min/kg (day 7) in full-term newborns [20].
There were linear relationships between serum creatinine concentration and levETIRAcetam
clearance and between creatinine clearance and levETIRAcetam clearance in a
pharmacokinetic study. Clearance was 1.21 L/min/kg in 18 newborns (32 weeks gestational
age or more) of median postnatal age 2 days (0 to 32 days) administered a single IV
levetiracetam dose [21].
Half-Life: 15.6 hours (day 1) and 9 hours (day 7) in full-term newborns [20].
There were linear relationships between serum creatinine concentration and levETIRAcetam
half-life in a pharmacokinetic study. Half-life was 8.9 hours in 18 newborns (32 weeks
gestational age or more) of median postnatal age 2 days (0 to 32 days) administered a single
IV levetiracetam dose [21].
ABOUT
Injection
Keppra® injection for intravenous use is available in single-use 5 mL vials containing 500 mg
(100 mg/mL). Must be further diluted to a concentration of 5 to 15 mg/mL in compatible
diluent prior to administration. Diluted solution is stable for 24 hours at room temperature
[5].
Oral Solution
Keppra® oral solution is available in a concentration of 100 mg/mL (dye- and alcohol-free).
Store at room temperature [7] .
Extemporaneous Suspension 50 mg/mL

LevETIRAcetam suspension was stable for 91 days at 4° C and 25° C stored in amber plastic
bottles prepared in Ora-Sweet and Ora-Plus [22]; for 95 days at 25° C stored in amber glass
bottles, plastic bottles, or plastic syringes; and stable at 4° C in amber glass or plastic bottles
when prepared in Oral Mix and Oral Mix SF.[23] :
Triturate 500 mg levETIRAcetam tablets
Resuspend the powder in vehicle (Oral Mix, Oral Mix SF, or 1:1 ratio of Ora-Sweet and
Ora Plus)
447
Levothyroxine
Dose
Hypothyroidism
Dosage should be individualized and adjusted based upon factors including patient age, body
weight, cardiovascular status, concomitant medical conditions, coadministered food, and the
specific nature of the condition being treated [1].
Peak therapeutic effect may not be attained for 4 to 6 weeks [1].
Initial oral dose: 10 to 15 mcg/kg/day orally [1]
Dosage Adjustments
At Risk of Cardiac Failure: Consider a lower starting dose and increase every 4 to 6 weeks
as needed based on clinical and laboratory response [1].
Initial IV dose: 5 to 8 mcg/kg/dose every 24 hours.
Uses

•Levothyroxine is indicated as a replacement or supplementation in patients with primary
(thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired
hypothyroidism in pediatric patients (Unithroid(R), Tirosint(R)-SOL and Synthroid(R)) [6][1]
[3] and in patients 6 years or older (Tirosint(R)) [7].
•As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-
dependent well-differentiated thyroid cancer. (Unithroid(R), Tirosint(R)-SOL and
Synthroid(R)) [6][1][3] and in patients 6 years or older (Tirosint(R)) [7].
Limitations of use
•Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in
iodine-insufficient patients or for the treatment of hypothyroidism during the recovery phase
of subacute thyroiditis [6][1][3][7].
Administration
Oral[2][3]
Single daily dose
Administer on an empty stomach; one-half to 1 hour before breakfast
.Should be separated by at least 4 hours from drugs that are known to impair its
absorption (eg, antacids, bile acid sequestrants, calcium carbonate, cation exchange
resins, ferrous sulfate, orlistat, sucralfate)
Solution: May administer directly into mouth by squeezing content of 1 single unit-dose
ampule into mouth or onto a spoon. May also administer in water by squeezing the contents
of 1 single unit-dose ampule into a cup of water; stir and drink immediately. Rinse cup with
https://www.micromedexsolutions.com/micromedex2/librarian/CS/2E5BFF/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
448
more water and drink. Do not dilute in other liquids or food. Open the ampule and prepare
the solution immediately before intake [1].
Tablets: May crush and suspend in 5 to 10 mL of water prior to administration (eg, for
infants and children who cannot swallow intact table); do not store suspension. Do not
suspend in other liquids or food (eg, soybean-based infant formula) [3]
Injection
Intravenous powder for solution: Final concentrations are approximately 20 mcg/mL or
100 mcg/mL. Do not add to any other IV solution [4].
Intravenous solution: Do not exceed an IV administration rate of 100 mcg/min. Do not
add to any other IV solution [5]
MEDICATION SAFETY
CONTRAINDICATIONS
•Hypersensitivity to thyroid hormone or any component of the product [8]
•Hypersensitivity to glycerol (oral solution) [9]
•Uncorrected adrenal insufficiency; may precipitate acute adrenal crisis [6][3][9][10]
PRECAUTIONS
Cardiovascular: New or worsening cardiac abnormalities, such as increase in heart rate,
angina and arrhythmias may develop with overtreatment; reduce or stop therapy for one
week and then cautiously restart at lower dose [6][3][9]
Cardiovascular: Underlying cardiovascular disease; initiate therapy at lower dose [6][3][9];
monitoring recommended [4]
Cardiovascular: Surgical procedures in patients with preexisting coronary artery disease
increases risk of cardiac arrhythmias; monitoring recommended [6][3][9][10]
Endocrine and metabolic: Use of doses above recommended range, including excessive
bolus doses greater than 500 mcg, increase risk of serious or life-threatening manifestations
of toxicity; monitoring recommended and consider dose adjustment [4]
Endocrine and metabolic: Chronic autoimmune thyroiditis, with progression to myxedema
or acute adrenal crisis, may occur in association with other autoimmune disorders, such as
adrenal insufficiency, diabetes mellitus, and pernicious anemia; treat with replacement
glucocorticoids prior to initiation of levothyroxine and monitoring is recommended [4]
Endocrine and metabolic: Oral therapy not recommended to treat myxedema coma [6][3]
[9]
Endocrine and metabolic: Concomitant adrenal insufficiency; treat with replacement
glucocorticoids prior to initiation of levothyroxine to avoid acute adrenal crisis [6][3][9]
Endocrine and metabolic: Worsening glycemic control in diabetic patients may occur;
monitoring recommended [6][3][9]
Musculoskeletal: Increased bone resorption and decreased bone mineral density may
occur with greater than replacement doses [1].
Adverse Effects
449
Prolonged over-treatment can produce premature craniosynostosis and acceleration of bone
age.
Black Box Warning
Thyroid hormones, including levothyroxine, either alone or with other therapeutic agents
should not be used for the treatment of obesity or for weight loss.
In euthyroid patients, doses within the range of daily hormonal requirements are ineffective
for weight loss.
Larger doses may produce serious or life-threatening manifestations of toxicity, especially
when given in combination with sympathomimetic amines such as those used for their
anorectic effects [3].
Monitoring
After 2 weeks of treatment, serum levothyroxine (T4) concentration should be in the high
normal range (10 to 16 mcg/dL) and should be maintained in this range for the first year of
life. Serum triiodothyronine (T3) concentration should be normal (70 to 220 nanograms/dL),
and TSH should have declined from initial value. After 12 weeks of treatment, serum TSH
concentration should be in the normal range, less than 15 milliunits/L. Serum T4 and TSH
concentrations should be measured at two weeks of age, then every 1 to 2 months, or 2
weeks after any change in dosage. Assess for signs of hypothyroidism: Lethargy, poor
feeding, constipation, intermittent cyanosis, and prolonged neonatal jaundice. Assess for
signs of thyrotoxicosis: hyperreactivity, altered sleep pattern, tachycardia, tachypnea, fever,
exophthalmos, and goiter. Periodically assess growth, development, and bone-age
advancement.
Pharmacology
Mechanism of action: Tissue deiodination converts T4 to T3, the active metabolite.
Bioavailability of oral levothyroxine is approximately 40% to 80%. Absorption increased in

fasting state. Circulating thyroid hormones are 99% bound to plasma proteins. Only unbound
hormone is metabolically active. Major pathway of metabolism is through deiodination. Also
metabolized via conjugation with glucuronides and sulfates playing a role. Primarily
eliminated in the urine with approximately 20% eliminated in the stool. Half-life is 6 to 7 days
for oral levothyroxine (T4), and 2 days or less for liothyronine (T3); peak therapeutic effect
may not be reached until 4 to 6 weeks due to its long half-life. Levothyroxine IV produces
effects in 6 to 8 hours, with full therapeutic effect within 24 hours. Levothyroxine IV also
produces a predictable hormone level in the reservoir with a 7 day half-life, thus no need for
multiple injections; daily injections of lesser amounts of levothyroxine are sufficient until daily
oral dose accepted by the patient [2] .
450
ABOUT
Oral
Availability: levothyroxine sodium 13 to 200 mcg/mL clear oral solution [9], scored tablets
ranging from 25 to 300 mcg per tablet [3]. Also available in capsules that contain a viscous
liquid ranging from 13 to 150 mcg per capsule. Capsules cannot be crushed, suspended
in water, or dissolved by placing in water before use. Monitor patient closely when
switching brand of drug due to some differences in bioavailability.
Extemporaneous Oral Suspension

•To prepare a 15-mcg/mL levothyroxine oral suspension: Crush levothyroxine 100-mcg
tablets in glycerol and add sterile water up to desired volume. Shake well before dispensing.
Product stability is 10 days when refrigerated between 2 and 8 degrees C. Stability tests
demonstrated a 12% decline in levothyroxine concentration in the prepared suspension over
11 days.
To prepare a 25 mcg/mL levothyroxine sodium suspension[11]:

Crush and grind 200 mcg levothyroxine tablets to a fine powder in a mortar with a
pestle.
Mix powder in a suitable vehicle suspension (1:10 Simple syrup NF and 1%
methylcellulose or 1:1 OraSweet and OraPlus).
When refrigerated at 4 degrees C in amber polyethylenephthalate bottles, the
suspension was stable for two weeks (14 days) and at 25 degrees C for up to one week
(7 days)
•An oral liquid formulation of levothyroxine sodium 25 mcg/mL in 40% glycerol

compounded from crushed tablets and distilled water with no preservatives added was stable
for 8 days when stored in amber bottles at 4 degrees C. Degradation occurred faster in the
formulation with preservative (methylparaben).
Injection
Powder for solution:Lyophilized powder in vials containing 100 or 500 mcg. Use only NS
for reconstitution. Following reconstitution with 5 mL of NS, final concentrations are
approximately 20 mcg/mL and 100 mcg/mL Use immediately. Do not add to any other
IV solution. Reconstituted solution is preservative free and stable for 4 hours [4].
Solution: Levothyroxine is available as a solution in single-dose vials containing 20, 40, or
100 mcg/mL [5]
451
Lidocaine - Antiarrhythmic
Dose
Initial bolus dose: 0.5 to 1 mg/kg IV push over 5 minutes. Repeat

every 10 minutes as necessary to control arrhythmia. Maximum total bolus dose should
not exceed 5 mg/kg.
Maintenance IV infusion: 10 to 50 mcg/kg/minute. Premature neonates should receive

lowest dosage.
Uses
Short-term control of ventricular arrhythmias, including ventricular tachycardia, premature

ventricular contractions, and arrhythmias resulting from digitalis intoxication.
Administration
The concentration for an IV push dose is 1 to 20 mg/mL. For continuous infusion, dilute in
compatible solution to concentration of 0.8 to 8 mg/mL or use available premixed solutions
(4 to 8 mg/mL) [1][2].
Solution Preparation Calculations

To calculate the AMOUNT of drug needed per defined final fluid volume:
Desired final concentration (mg/mL) x defined final fluid volume (mL) = AMOUNT of drug to
add to final infusion solution (mg).
To calculate the VOLUME of drug needed per defined final fluid volume:
*AMOUNT of drug to add (mg) ÷ drug (vial) concentration (mg/mL) = VOLUME of drug to
add (mL)
Example (for Lidocaine): Mix 50 mL of 2400 mcg/mL solution using lidocaine
concentration of 20 mg/mL.
2400 mcg/mL = 2.4 mg/mL
2.4 mg/mL x 50 mL = 120 mg lidocaine
*120 mg ÷ 20 mg/mL = 6 mL of lidocaine
Add 6 mL of lidocaine (20 mg/mL) to 44 mL of compatible solution (eg, D5W) to yield 50 mL
of infusion solution with a concentration of 2400 mcg/mL.
Lidocaine Titration Chart

Concentration Dose IV Rate
(mcg/mL) (mcg/kg/min) (mL/kg/hour)
800 10 0.75
20 1.5
https://www.micromedexsolutions.com/micromedex2/librarian/CS/8C59DD/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
452
30 2.25
40 3
50 3.75
10 0.375
20 0.75
1600 30 1.125
40 1.5
50 1.875
10 0.25
20 0.5
2400 30 0.75
40 1
50 1.25
10 0.15
20 0.3
4000 30 0.45
40 0.6
50 0.75
10 0.1
20 0.2
6000 30 0.3
40 0.4
50 0.5
10 0.075
20 0.15
8000 30 0.225
40 0.3
50 0.375
MEDICATION SAFETY
CONTRAINDICATIONS
•Complete heart block and wide complex tachycardia attributable to accessory conduction
pathways [4][5].
•Stokes-Adams syndrome[6].
•Wolff-Parkinson-White Syndrome [6].
•Severe degrees of sinoatrial, atrioventricular, or intraventricular block [6].
•Known hypersensitivity to local anesthetics of the amide type [6]
PRECAUTIONS
Cardiovascular: Acceleration of ventricular rate may occur, particularly in patients with
atrial fibrillation or flutter [6]
Cardiovascular: More frequent or serious ventricular arrhythmias or complete heart block
may occur in patients with sinus bradycardia, or incomplete heart block without prior
acceleration in heart rate [6]
Endocrine and metabolic: Malignant hyperthermia may occur; discontinue use
immediately and institute countermeasures [6]
Hematologic: Methemoglobinemia has been reported with local anesthetic use; increased risk
in patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic
methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and
453
concurrent exposure to oxidizing agents or their metabolites; close monitoring recommended
in these patients [7]
Hepatic: Possible increased risk of toxicity in patients with impaired hepatic function [6]
Immunologic: Hypersensitivity reactions have been reported; immediate discontinuation
required [6]
Musculoskeletal: Chondrolysis may occur with intraarticular infusions following
arthroscopic or other surgical procedures (unapproved use) [8]
Renal: Possible increased risk of toxicity in patients with impaired renal function [6]
Special Populations: Viscous lidocaine is not recommended or approved for teething pain
[9][10]. Seizures, cardiopulmonary arrest, and death have been associated with the use of
viscous lidocaine for teething pain or oral irritation in infants and children [11][12][13].
Adverse Effects
Early signs of CNS toxicity are drowsiness, agitation, vomiting, and muscle twitching. Later
signs include seizures, loss of consciousness, respiratory depression, and apnea. Cardiac
toxicity is associated with excessive doses and includes bradycardia, hypotension, heart
block, and cardiovascular collapse.
D5W, D10W, and NS.
Alteplase, aminophylline, amiodarone, ampicillin, caffeine citrate, calcium chloride, calcium

gluconate, cefazolin, cefoxitin, chloramphenicol, cimetidine, dexamethasone, digoxin,
dobutamine, dopamine, enalaprilat, erythromycin lactobionate, famotidine, fentanyl,
flumazenil, furosemide, glycopyrrolate, heparin, hydrocortisone succinate, insulin, linezolid,
methicillin, metoclopramide, micafungin, morphine, nafcillin, nicardipine, nitroglycerin,
penicillin G, pentobarbital, potassium chloride, procainamide, ranitidine, sodium bicarbonate,
and sodium nitroprusside.
Phenytoin.
Monitoring
454
Continuous monitoring of ECG, heart rate, and blood pressure should be performed. Assess
level of consciousness. Observe for seizure activity. Therapeutic drug concentration is 1.5 to
6 mg/L, with toxicity associated with concentrations greater than 9 mg/L [3][2].
Pharmacology
Lidocaine is a type 1b antiarrhythmic agent used intravenously. Onset of action is 1 to 2

minutes after bolus administration. Plasma half-life in neonates is 3 hours. Free drug fraction
in both term and premature neonates is approximately twice that found in older children
because of significantly reduced protein binding by α1-acid glycoprotein. Transformed in the
liver to metabolites with antiarrhythmic activity; approximately 30% is excreted unchanged in
neonates.
ABOUT
Use only preservative-free lidocaine without EPINEPHrine.

Availability: Multiple concentrations ranging from 1% to 20%. Concentrations of 10% (100
mg/mL) and 20% (200 mg/mL) must be diluted [6][8]. Premixed solutions for continuous
infusion, 4 mg/mL (0.4%) and 8 mg/mL (0.8%) [6].
Storage: Store at a room temperature of 20 to 25 degrees C [6]. Avoid excessive heat [6]
and protect from light [8]
Dilution: To make a dilution for bolus dosing, dilute 10 mg lidocaine (0.5 mL of 2%
solution) in 9.5 mL NS or D5W, yielding a 1-mg/mL final concentration.
455
Lidocaine - CNS
Dose
Term, normothermic newborns:

Loading dose: 2 mg/kg IV, followed immediately by maintenance infusion.
Maintenance infusion: 6 mg/kg per hour for 6 hours, then 4 mg/kg per hour for 12 hours,
then 2 mg/kg per hour for 12 hours.
Caution: Preterm newborns and term newborns undergoing hypothermia treatment are at
risk for drug accumulation due to slower drug clearance. Precise dosing in these infants is
uncertain.
Uses
Treatment of severe recurrent or prolonged seizures that do not respond to first-line

therapies.
Administration
Administer loading dose as an IV bolus over 10 minutes at a concentration not exceeding 20

mg/mL. For continuous infusion, dilute in compatible diluent to a concentration of 0.8 to not
exceeding 8 mg/mL or use available premixed solutions (4 to 8 mg/mL) [1][2][3].
MEDICATION SAFETY
CONTRAINDICATIONS
•Complete heart block and wide complex tachycardia attributable to accessory conduction
pathways [4][5].
•Stokes-Adams syndrome[6].
•Wolff-Parkinson-White Syndrome [6].
•Severe degrees of sinoatrial, atrioventricular, or intraventricular block [6].
•Known hypersensitivity to local anesthetics of the amide type [6]
PRECAUTIONS
Cardiovascular: Acceleration of ventricular rate may occur, particularly in patients with
atrial fibrillation or flutter [6]
Cardiovascular: More frequent or serious ventricular arrhythmias or complete heart block
456
may occur in patients with sinus bradycardia, or incomplete heart block without prior
acceleration in heart rate [6]
Endocrine and metabolic: Malignant hyperthermia may occur; discontinue use
immediately and institute countermeasures [6]
Hematologic: Methemoglobinemia has been reported with local anesthetic use; increased
risk in patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic
methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and
concurrent exposure to oxidizing agents or their metabolites; close monitoring recommended
in these patients [7]
Hepatic: Possible increased risk of toxicity in patients with impaired hepatic function [6]
Immunologic: Hypersensitivity reactions have been reported; immediate discontinuation
required [6]
Musculoskeletal: Chondrolysis may occur with intraarticular infusions following
arthroscopic or other surgical procedures (unapproved use) [8]
Renal: Possible increased risk of toxicity in patients with impaired renal function [6]
Special Populations: Viscous lidocaine is not recommended or approved for teething pain
[9][10]. Seizures, cardiopulmonary arrest, and death have been associated with the use of
viscous lidocaine for teething pain or oral irritation in infants and children [11][12][13].
Adverse Effects
Do not use concurrently with phenytoin due to cardiac effects. Stop infusion immediately if
significant cardiac arrhythmia occurs. Arrhythmias and significant bradycardia have occurred
in 5% of reported cases. Slowing of the heart rate is common.
In a retrospective study (n=521), the incidence of cardiac events with lidocaine treatment for
seizures in term and preterm infants was 1.3% to 1.9%. Cardiac events included bradycardia
(n=6) with 2:1 AV block in 2 infants and QRS prolongation in 1 infant. Irregular heart rate
occurred in 2 infants, decreased heart rate not fulfilling bradycardia criteria occurred in 3,
with a prolonged QT interval in 1 infant, and ventricular extrasystoles were reported in 2
infants. Tachycardia, hypotension, and asystole following bradycardia were reported in 1
infant each [14].
D5W, D10W, and NS.
Alteplase, aminophylline, amiodarone, ampicillin, caffeine citrate, calcium chloride, calcium

gluconate, cefazolin, cefoxitin, chloramphenicol, cimetidine, dexamethasone, digoxin,
dobutamine, dopamine, enalaprilat, erythromycin lactobionate, famotidine, fentanyl,
flumazenil, furosemide, glycopyrrolate, heparin, hydrocortisone succinate, insulin, linezolid,
metoclopramide, micafungin, morphine, nafcillin, nicardipine, nitroglycerin, penicillin G,
pentobarbital, potassium chloride, procainamide, ranitidine, sodium bicarbonate, and sodium
457
nitroprusside.
Phenytoin.
Monitoring
Continuous monitoring of EKG, heart rate, and blood pressure. Observe for worsening of
seizure activity. Measuring blood concentrations is not clinically useful except when
accumulation is suspected.
Pharmacology
The mode of action for lidocaine as an anticonvulsant drug is unknown. Lidocaine is

metabolized in the liver into 2 active metabolites: monoethylglycinexylidide (MEGX) and
glycinxylidide (GX). Approximately 30% is excreted unchanged in the urine. The half-life in
neonates is at least 3 hours, and clearance is dose-dependent. The clinically effective dose of
6 mg/kg/hr will lead to accumulation of both lidocaine and metabolites within several hours.
Free drug fraction in both term and premature neonates is approximately twice that found in
older children because of significantly reduced protein binding by alpha 1-acid glycoprotein.
ABOUT
Use only preservative-free lidocaine without EPINEPHrine.

Availability: Multiple concentrations ranging from 1% to 20%. Concentrations of 10% (100
mg/mL) and 20% (200 mg/mL) must be diluted [6][8]. Premixed solutions for continuous
infusion, 4 mg/mL (0.4%) and 8 mg/mL (0.8%) [6].
Storage: Store at a room temperature of 20 to 25 degrees C [6]. Avoid excessive heat [6]
and protect from light [8]
Dilution: To make a dilution for bolus dosing, dilute 10 mg lidocaine (0.5 mL of 2%
solution) in 9.5 mL NS or D5W, yielding a 1-mg/mL final concentration.
458
Lidocaine/Prilocaine
Dose
Do not use in infant younger than 12 months who is receiving treatment with
methemoglobin-inducing agents which include drugs in classes of nitrates/nitrites, local
anesthetics, antineoplastic agents, antibiotics, antimalarials, anticonvulsants, and other
drugs[1]
37 weeks' gestation or older:Maximum total dose of 1 g applied to maximum
application area of 10 cm2 for maximum application time of 1 hour [1]
Uses

Topical anesthetic for use on normal intact skin for local analgesia and genital mucous
membranes for superficial minor surgery and as pretreatment for infiltration anesthesia [1].
Not recommended for any clinical situation where penetration or migration beyond the
tympanic membrane into the middle ear is possible due to risk of ototoxic effects [1]
Evaluated in 105 full-term neonates for blood drawing and circumcision procedures. Studies
have not demonstrated efficacy for heel lancing [1].
MEDICATION SAFETY
CONTRAINDICATIONS
Hypersensitivity to local amide-type anesthetics or to any component of the product [1]
PRECAUTIONS
Concomitant Use: with class III anti-arrhythmic drugs (e.g. amiodarone, bretylium, sotalol,
dofetilide) may result in additive cardiac effects; monitoring recommended [1].
Dermatologic: Increased risk for systemic absorption and toxicity with covering of
application site, large doses and/or treatment areas, skin temperature increases, and with
irritated, broken skin, or wounds; potentially resulting in life-threatening side effects [2][3]
Hematologic: Methemoglobinemia has been reported with use of local anesthetics;
increased risk in patients with glucose-6-phosphate dehydrogenase deficiency, congenital or
idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of
age, and concurrent exposure to oxidizing agents or their metabolites and other drugs
associated with methemoglobinemia; if use is required in at-risk patients monitoring is
recommended; medical management and discontinuation of therapy is required [1].
Hepatic: Risk of toxic plasma concentrations in patients with severe hepatic disease [1]
Immunologic: Use with caution in patients with history of allergies to paraaminobenzoic
459
acid derivatives (procaine, tetracaine, benzocaine, etc.) [1]
Immunologic: Has been shown to inhibit viral and bacterial growth, effect on intradermal
injections of live vaccines has not been determined [1]
Ophthalmic: Avoid contact with eyes due to risk of severe irritation and loss of protective
reflexes [1]
Otic: Ototoxic effects possible when drug penetrates beyond the tympanic membrane into
the middle ear [1]
Special populations: Acutely ill or debilitated patients; increased sensitivity to systemic
effects [1]
Adverse Effects
Blanching and redness resolve without treatment. When measured, blood levels of
methemoglobin in neonates after the application of 1 g of EMLA cream have been well below
toxic levels. Two cases of methemoglobinemia in infants occurred after greater than 3 g of
EMLA cream was applied; in 1 of these cases, the infant also was receiving sulfamethoxazole.
EMLA cream should not be used in neonates with congenital or idiopathic
methemoglobinemia, or who are receiving other drugs known to induce methemoglobinemia:
sulfonamides, acetaminophen, nitrates, nitroglycerin, nitroprusside, phenobarbital, and
phenytoin.
Monitoring
Blood methemoglobin concentration if concerned about toxicity.
Pharmacology
EMLA cream, containing 2.5% lidocaine and 2.5% prilocaine, attenuates the pain response to
circumcision when applied 60 to 90 minutes before the procedure. The analgesic effect is
limited during the phases associated with extensive tissue trauma such as during lysis of
adhesions and tightening of the clamp. Stabilizes the neuronal membranes by inhibiting the
ionic fluxes required for conduction and initiation of nerve impulses. There is a theoretic
concern about the potential for neonates to develop methemoglobinemia after the
application of EMLA cream, because a metabolite of prilocaine can oxidize hemoglobin to
methemoglobin. Neonates are deficient in methemoglobin NADH cytochrome b5 reductase.
Lidocaine is metabolized rapidly by the liver to a number of active metabolites and then
excreted renally.
ABOUT
460
Available in 5-g and 30-g tubes with Tegaderm dressing. Each gram of EMLA contains
lidocaine 25 mg and prilocaine 25 mg in a eutectic mixture. pH of the product is 9. Contains
no preservatives.
461
Linezolid
Dose
Usual dose, 10 mg/kg/dose IV or orally every 8 hours [1][2].

Preterm newborns less than 1 week of age: 10 mg/kg/dose IV or orally every 12 hours
[1].
Anthrax[3]
32 up to 34 weeks gestational age
0 to 1 week: 10 mg/kg/dose IV or oral every 12 hours.
1 to 4 weeks: 10 mg/kg/dose IV or oral every 8 hours.
34 weeks or more gestational age
0 to 4 weeks: 10 mg/kg/dose IV or oral every 8 hours
Duration: 2 to 3 weeks or more until stable as IV triple therapy for systemic anthrax
(anthrax meningitis or disseminated infection and meningitis cannot be ruled out) or as IV
combination therapy for systemic anthrax when meningitis is ruled out. Continue
antimicrobial course of prophylaxis (usually oral therapy) for up to 60 days from onset of
illness [3].
Uses
Limited to treatment of infections, including endocarditis and ventriculitis, caused by gram

positive organisms (eg, methicillin-resistantStaph. aureus, , penicillin-resistant Strep.
pneumoniae , and vancomycin-resistant Enterococcus faecium) that are refractory to
conventional therapy with vancomycin and other antibiotics [4][5][6][2]. Do not use as
empiric treatment or in any patient with infections caused by gram-negative organisms.
Anthrax: Intravenous linezolid is recommended for neonates 32 week gestational age or

older for the following [3]:
Systemic Anthrax when meningitis can be ruled out (IV)

Combination IV Therapy
Preferred: Ciprofloxacin. Alternatives in order of preference: meropenem, levofloxacin,
imipenem/cilastatin, or vancomycin. If strains are penicillin-susceptible, then penicillin G
(preferred) or ampicillin (alternative).
Plus
Preferred: Clindamycin Alternatives in order of preference: linezolid, doxycycline (not
for neonates 37 weeks gestation or younger), or rifampin.
Systemic Anthrax (meningitis or disseminated infection and meningitis cannot be
ruled out) (IV)
Triple IV Therapy
Preferred: Ciprofloxacin. Alternatives in order of preference: levofloxacin or
moxifloxacin
Plus
Preferred: Meropenem. Alternatives in order of preference: imipenem/cilastatin or
doripenem. If strains are penicillin-susceptible, then penicillin G (preferred) or ampicillin
(alternative).
Plus
Preferred: Linezolid. Alternatives in order of preference: clindamycin or rifampin or as
a last resort, chloramphenicol
Oral follow-up therapy for severe anthrax
462
Combination Oral Therapy
Preferred: Ciprofloxacin. Alternative: levofloxacin. If strains are penicillin- susceptible,
amoxicillin (preferred) or penicillin VK (alternative).
Plus
Preferred: Clindamycin.Alternatives in order of preference: doxycycline (not for
neonates 37 weeks gestation or younger) or linezolid.
Administration
IV: Give as an intermittent IV infusion over 30 to 120 minutes. Supplied as ready-to-use

infusion bags (2 mg/mL); no further dilution is necessary [1].
Oral: May administer without regard to timing of feedings. Before administering oral
suspension, gently mix by inverting bottle 3 to 5 times. Do not shake [1].
MEDICATION SAFETY
Contraindicated in patients with carcinoid syndrome, uncontrolled hypertension,

pheochromocytoma, thyrotoxicosis, and/or patients receiving concurrent serotonergic agents,
sympathomimetic agents, vasopressive agents, or dopaminergic agents unless monitored
closely [1].
Use not recommended in pediatric patients with central nervous system (CSF) infections due
to variable linezolid CSF concentrations. Myelosuppression (including anemia, leukopenia,
pancytopenia, and thrombocytopenia) has been reported. Symptomatic hypoglycemia has
been reported in patients with diabetes receiving insulin. Serotonin syndrome may occur with
concurrent use of serotonergic agents. Peripheral and optic neuropathy have been reported
in pediatric patients, mainly in patients treated for longer than 28 days. Convulsions have
been reported [1].
Lactic acidosis has been reported in a case series of 3 children aged 6 months, 6 months,
and 16 years receiving linezolid for 53, 31 and 7 days of treatment, respectively. All 3
children had liver dysfunction and complicated medical courses while receiving linezolid
therapy. Two patients developed multiple system organ failure and metabolic acidosis, and
the third patient developed pressor-refractory shock and metabolic acidosis. The role of
linezolid in the development of lactic acidosis in these patients is unknown [7].
Safety and efficacy of linezolid therapy for greater than 28 days has not been evaluated in
controlled clinical trials [1].
The FDA issued an alert regarding Zyvox (linezolid) on March 16, 2007. Patients in
an open-label, randomized trial comparing linezolid with vancomycin, oxacillin, or dicloxacillin
in the treatment of seriously ill patients with intravascular catheter-related bloodstream
infections had a higher chance of death than did patients treated with any comparator
antibiotic, and the chance of death was related to the type of organism causing the infection.
Patients with Gram positive infections had no difference in mortality according to their
antibiotic treatment. In contrast, mortality was higher in patients treated with linezolid who
were infected with Gram negative organisms alone, with both Gram positive and Gram
negative organisms, or who had no infection when they entered the study. See
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm101503.htm.
Adverse Effects
Elevated transaminases and diarrhea occur in approximately 5% of treated patients;

thrombocytopenia and anemia occur in 2% to 5% [2][9].
Sideroblastic anemia and severe cutaneous adverse reactions such as toxic epidermal
necrolysis and Stevens-Johnson syndrome have been reported during postmarketing
463
surveillance [10].
D5W, NS, Lactated Ringers.
Acyclovir, amikacin, aminophylline, ampicillin, aztreonam, calcium gluconate, caspofungin,

cefazolin, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, cimetidine, clindamycin,
dexamethasone, digoxin, dobutamine, dopamine, enalaprilat, esmolol, famotidine, fentanyl,
fluconazole, furosemide, ganciclovir, gentamicin, heparin, hydrocortisone succinate,
imipenem/cilastatin, lidocaine, lorazepam, magnesium sulfate, meropenem,
methylprednisolone, metoclopramide, metronidazole, mezlocillin, midazolam, morphine,
naloxone, netilmicin, nicardipine, nitroglycerin, pentobarbital, phenobarbital, piperacillin,
piperacillin-tazobactam, potassium chloride, propranolol, ranitidine, remifentanil, sodium
bicarbonate, theophylline, ticarcillin, tobramycin, vancomycin, vecuronium, and zidovudine.
Amphotericin B, erythromycin lactobionate, phenytoin, and trimethoprim/sulfamethoxazole.
Monitoring
Monitor CBC weekly, especially in patients receiving linezolid for longer than 2 weeks, those
with myelosuppression, those receiving concurrent myelosuppressive drugs, or those with a
chronic infection who have received previous or concomitant antibiotic therapy [1]. Monitor
lactate concentrations in patients receiving extended courses of linezolid therapy or in
patients with pre-existing hepatic or renal dysfunction [7]. Patients receiving an extended
course of therapy (eg, over 28 days) should be monitored for signs and symptoms of
neuropathy [8]. Monitor for signs and symptoms of serotonin syndrome (hyperpyrexia,
hyperreflexia, and incoordination) in patients receiving concomitant serotonergic agents.
Visual function should be assessed in patients receiving long-term linezolid (3 months or
greater) and in all patients experiencing visual impairment. Monitor blood pressure in
patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, and/or in
patients receiving sympathomimetic agents, vasopressive agents, or dopaminergic agents
[1].
Pharmacology
Linezolid is an oxazolidinone agent that has a unique mechanism of inhibition of bacterial

protein synthesis. It is usually bacteriostatic, although it may be bactericidal against S.
pneumoniae B. fragilis C. perfringens
, , and . Resistance to linezolid has been reported for
vancomycin-resistant E. faecium S. aureus
and methicillin-resistant [11][12][13][14][15].
S. aureus S. epidermidis S. haemolyticus
Outbreaks of linezolid-resistant , , and have been
reported in adult ICU settings. The majority of patients had received linezolid previously [16]
[17][11].
Rapidly penetrates osteoarticular tissues and synovial fluid. CSF concentrations were 70% of
464
plasma concentrations in older patients with non-inflamed meninges. Completely and rapidly
absorbed when administered orally to adults and children. Metabolized by oxidation without
cytochrome CYP induction. Excreted in the urine as unchanged drug (30%) and two inactive
metabolites. Serum half-life in most neonates is 2 to 3 hours, with the exception of preterm
neonates less than one week of age, who have a serum half-life of 5 to 6 hours [1][18][19].
Neonate study: Linezolid plasma concentrations were greater or equal to the MIC (1 to 2
mg/L) in 15 of 16 extremely premature (mean gestational age, 28 weeks) neonates (mean
postnatal age at beginning of treatment, 3 weeks) administered either oral or IV linezolid.
The dosages of linezolid were 10 mg/kg orally every 8 hours or 30 mg/kg/day by continuous
IV. Trough concentrations were measured for the oral route [20].
ABOUT
Linezolid IV injection is supplied as a 2-mg/mL solution in single-use, ready-to-use 100-

mL, 200-mL, and 300-mL plastic infusion bags in a foil laminate overwrap. Keep in the
overwrap until use. Store at room temperature.Do not freeze. IV injection may exhibit a
yellow color that can intensify over time without affecting potency [1].
An oral suspension is available, and after reconstitution with 123 mL of distilled water (in 2
portions) provides 20 mg/mL. Store at room temperature. Use within 21 days after
reconstitution. Protect from light [1].
465
Lopinavir/Ritonavir
Dose
HIV Infection
14 days or older: Lopinavir 16 mg/ritonavir 4 mg/kg orally twice daily OR lopinavir 300
mg/ritonavir 75 mg/m2 orally twice daily [1][2][3].
Do not use until a postmenstrual age of 42 weeks [2].
Once-daily lopinavir/ritonavir is NOT recommended in any pediatric patient [2].
Co-administration with efavirenz, nevirapine, or nelfinavir is NOT recommended

in patients younger than 6 months of age [4].
When used in infants and young children, especially those 14 days to 6 months of age, it is
critical to ensure that dose calculation, transcription of the medication order, and dosing
instructions are accurate, and that total amounts of alcohol and propylene glycol from all
concomitant medications are accounted for. Oral solution contains ethanol (42.4% v/v) and
propylene glycol (15.3% w/v) [4].
Uses
Risk of HIV
in Newborn
Low risk of
transmission
to the regimen
Higher risk
of
transmission
breastfeeding #
466
Confirmed •Confirmed positive newborn HIV •3-drug regimen (zidovudine, lamiVUDine, and
virologic test/nucleic acid test. nevirapine) at treatment dosage OR
•3-drug regimen (zidovudine, lamiVUDine and
raltegravir)
KEY
delivery.

Lopinavir/ritonavir is indicated in combination with other antiretroviral agents for the
treatment of HIV-1 infection in patients 14 days of age or older [4].
Administration
Administer with a feeding. Use a calibrated dosing syringe to administer the oral solution
dose [4].
If coadministered with didanosine, give didanosine 1 hour before or 2 hours after
lopinavir/ritonavir dose [4].
Oral solution not recommended for use with polyurethane feeding tubes due to ethanol and
propylene glycol content and potential for incompatibility. Compatible feeding tubes include
silicone and polyvinyl chloride (PVC) [5].
MEDICATION SAFETY
CONTRAINDICATIONS
•Concomitant use with the following alpha 1-adrenoreceptor antagonist: Alfuzosin [7]
•Concomitant use with the following antianginal agent: Ranolazine [7]
•Concomitant use with the following antiarrhythmic agent: Dronedarone [7]
•Concomitant use with the following anti-gout agent: Colchicine [7]
•Concomitant use with the following antimycobacterial agent: Rifampin [7]
•Concomitant use with the following antipsychotics: Lurasidone, pimozide [7]
•Concomitant use with the following ergot derivatives: Dihydroergotamine, ergotamine,
methylergonovine [7]
•Concomitant use with the following GI motility agent: Cisapride [7]
•Concomitant use with the following hepatitis C direct-acting antiviral agent:
Elbasvir/grazoprevir [7]
•Concomitant use with the following herbal product: St. John's wort (Hypericum perforatum)
[7]
•Concomitant use with the following HMG-CoA reductase inhibitors: Lovastatin, simvastatin
[7]
467
•Concomitant use with the following microsomal triglyceride transfer protein (MTTP)
inhibitor: Lomitapide [7]
•Concomitant use with the following phosphodiesterase type-5 (PDE5) inhibitor: Sildenafil
(when used for the treatment of pulmonary arterial hypertension) [7]
•Concomitant use with the following sedative/hypnotic agents: Triazolam, oral midazolam [7]
PRECAUTIONS
Cardiovascular: Avoid use in patients with congenital long QT syndrome or hypokalemia, as
QT interval prolongation and torsade de pointes have been reported [8].
Cardiovascular: PR interval prolongation and 2nd or 3rd degree atrioventricular block have
been reported [8].
Cardiovascular: Underlying structural heart disease, conduction system abnormalities,
ischemic heart disease, or cardiomyopathies; increased risk of conduction abnormalities [8]
Concomitant use: Avoid once-daily use with carbamazepine, efavirenz, nevirapine,
nelfinavir, phenobarbital, or phenytoin [8].
Concomitant use: Avoid use with avanafil, boceprevir, rivaroxaban, salmeterol, simeprevir,
tipranavir [9], amiodarone, or rifapentine [10].
Concomitant use: Avoid use with fluticasone or other glucocorticoids [8] , budesonide
(systemic, inhaled, or intranasal), or prednisone [10] unless benefit outweighs risk of
systemic corticosteroid side effects [10][8].
Concomitant use: Avoid use with QT interval-prolonging drugs [8].
Concomitant use: Avoid use with voriconazole unless benefit outweighs risk of decreased
voriconazole efficacy [8].
Endocrine and metabolic: New onset diabetes mellitus, exacerbation of preexisting
diabetes mellitus, hyperglycemia, and diabetic ketoacidosis have been reported with protease
inhibitor use; consider monitoring for hyperglycemia and new onset or exacerbation of
diabetes mellitus [6].
Endocrine and metabolic: Large elevations of triglycerides and cholesterol have been
reported; monitoring recommended [8].
Gastrointestinal: Pancreatitis has been reported, especially in patients with marked
triglyceride elevations and in patients with a history of pancreatitis [8].
Hematologic: Hemophilia type A or B; increased bleeding (eg, skin hematomas,
hemarthrosis) has been reported [8]
Hepatic: New or worsening of transaminase elevations or hepatic decompensation may
occur in patients with hepatitis B or C or with marked transaminase elevation; monitoring
recommended [8]
Hepatic: Hepatic dysfunction, including some fatalities, has been reported; monitoring
recommended [8].
Immunologic: Autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barre
syndrome) have been reported in the setting of immune reconstitution and may occur many
months after initiation of therapy [8].
Immunologic: Immune reconstitution syndrome may occur, leading to an inflammatory
response in patients with indolent or residual opportunistic infections [8].
Preterm neonates: Use of the oral solution in preterm neonates in the immediate postnatal
period is not recommended due to potential adverse effects caused by propylene glycol
accumulation (complete AV block, bradycardia, cardiomyopathy, lactic acidosis, acute renal
failure, CNS depression, and respiratory complications); if use is required, monitoring
recommended [8].
Adverse Effects
468
In a study of pediatric patients 6 months to 12 years of age (n=100), taste aversion (22%),
vomiting (21%), and diarrhea (12%) were the most commonly reported events in patients
treated for up to 48 weeks. Rash of moderate to severe intensity was reported in 3% of
patients [4]. Premature infants experience increased risk of toxicity, including life-threatening
cardiotoxicity [1].
Monitoring
[1]
1 to 2 2 to 4
†
Adverse
X X X X X
Effects ††
Adherence
††
CBC with
differential X X X X
¶
Chemistries
X X X X
‡¶
Random
Plasma X X
Glucose
Urinalysis X X♦
CD4 count
X X¶ X
†† ♦♦
HIV RNA
X X X X
††
Resistance
X ¶¶ X
Testing
Hepatitis B
screening X X
≈
469
Consider monitoring for hyperglycemia or new onset or worsening diabetes mellitus during
treatment with lopinavir/ritonavir [6].
Pharmacology
Lopinavir inhibits the HIV protease and prevents cleavage of the Gag-Pol polyprotein, thus
reducing the probability of viral particles reaching a mature, infectious state. Ritonavir is
administered solely to increase lopinavir plasma levels. Tmax following oral administration of
lopinavir/ritonavir is approximately 4 hours. Food increases bioavailability of oral solution;
therefore, lopinavir/ritonavir oral solution should be administered with feedings. Protein
binding is approximately 98% to 99% and is primarily to alpha-1-acid glycoprotein (higher
affinity) and albumin. Lopinavir is extensively metabolized in the liver, primarily by the
CYP3A4 enzyme system. Ritonavir is a potent inhibitor of CYP3A4 and inhibits the metabolism
of lopinavir, thereby increasing lopinavir concentrations. There are many drug interactions
with lopinavir involving CYP3A4. Approximately 2% and 20% of lopinavir is excreted
unchanged in the urine and feces, respectively [4]. In HIV-infected infants less than 6 weeks
of age (range, 3.6 to 5.9 weeks) receiving oral solution of lopinavir 300 mg/ritonavir 75
mg/m2 twice daily, the mean elimination half life was 3.7 hours (range 2.1 to 5.8 hours;
n=9), according to a prospective, phase I/II, open-label study [3]. A pharmacokinetic study
showed that the clearance of lopinavir/ritonavir was dependent on weight and postmenstrual
age in neonates and infants from birth to less than 2 years of age (weight range from 1.16 to
10.4 kg; n=96) [11].
ABOUT
Availability: Oral solution in a concentration of 80 mg lopinavir/20 mg ritonavir per mL that

also contains 42.4% alcohol (v/v) and propylene glycol (15.3% w/v).
Storage: Preferably, store oral solution refrigerated. Refrigerated oral solution is stable until
the expiration date printed on the label; if stored at room temperature up to 25 degrees C
(77 degrees F), oral solution should be used within 2 months [4].
470
471
LORazepam
Dose
0.05 to 0.1 mg/kg per dose IV slow push. Repeat doses based on clinical response.
Uses
Anticonvulsant, acute management of patients with seizures refractory to conventional

therapy.
Administration
Intravenous: For intermittent IV use, a concentration of 1 or 2 mg/mL should be infused at

a rate not to exceed 2 mg per minute. Avoid intra-arterial administration and perivascular
extravasation [1]. In neonates, it might be more practical to use concentrations such as 0.2
mg/mL or 0.4 mg/mL.
MEDICATION SAFETY
Contraindicated in premature infants as product contains benzyl alcohol. Use is also

contraindicated in patients with known sensitivity to benzodiazepines, polyethylene glycol,
propylene glycol, and benzyl alcohol; acute narrow-angle glaucoma; sleep apnea syndrome;
severe respiratory insufficiency unless mechanically ventilated. Intra-arterial
administration is also contraindicated. Not recommended for use in patients with
hepatic and/or renal failure [2].
Neurologic: Brain development in children may be affected by repeated or lengthy use of

general anesthetic and sedation drugs during surgeries or procedures, especially in children
younger than 3 years or in fetuses of pregnant women during the third trimester; balance
appropriate anesthesia use and timing of elective procedures that can be delayed against
potential risks in children younger than 3 years and pregnant women, particularly with
procedures that are longer than 3 hours or multiple procedures [2][3].
Special populations: Neonate patients are at increased risk of fatal "gasping syndrome"
with injection due to benzyl alcohol component, especially with higher doses and in
premature or low-birth-weight infants [2].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/15A1D5/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
472
Adverse Effects
Respiratory depression. Rhythmic myoclonic jerking has occurred in premature neonates

receiving LORazepam for sedation.
Black Box Warning
Risks From Concomitant Use With Opioids

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory
depression, coma, and death. Monitor patients for respiratory depression and sedation [2].
D5W, NS, and sterile water for injection.
Acyclovir, amikacin, amiodarone, bumetanide, cefepime, cefotaxime, cimetidine,

dexamethasone, dobutamine, dopamine, epinephrine, erythromycin lactobionate, famotidine,
fentanyl, fluconazole, fosphenytoin, furosemide, gentamicin, heparin, hydrocortisone
succinate, labetalol, levetiracetam, linezolid, methadone, metronidazole, midazolam,
milrinone, morphine, nicardipine, nitroglycerin, pancuronium bromide, piperacillin,
piperacillin-tazobactam, potassium chloride, propofol, ranitidine, remifentanil, trimethoprim-
sulfamethoxazole, vancomycin, vecuronium, and zidovudine.
Fat emulsion. Aztreonam, caffeine citrate, and imipenem/cilastatin.
Monitoring
Monitor respiratory status closely. Observe IV site for signs of phlebitis or extravasation.
Pharmacology
473
Dose-dependent CNS depression. Onset of action within 5 minutes; peak serum
concentration within 45 minutes. Duration of action is 3 to 24 hours. Mean half-life in term
neonates is 40 hours. Metabolized to an inactive glucuronide, which is excreted by the
kidneys. Highly lipid-soluble.
ABOUT
Injection available in 2-mg/mL and 4-mg/mL concentrations (1-mL preservative-free vial and
10-mL multidose vials) [1].
Limited data are available for neonates. Some available products contain 2% (20 mg/mL)
benzyl alcohol and 18% polyethylene glycol 400 in propylene glycol. For intermittent IV use,
must be diluted with an equal volume of compatible diluent; resultant concentration is 1
mg/mL and 2 mg/mL for the 2 mg/mL and 4 mg/mL concentrations, respectively [1] One
possible concentration for ease of measuring a dose would be 0.4 mg/mL; prepare by adding
1 mL of 4 mg/mL concentration in 9 mL of preservative-free sterile water for injection. In
products that contain benzyl alcohol, use of the 4 mg/mL vial will reduce the amount of
benzyl alcohol per dose compared with the 2 mg/mL vial.
Solutions should not be used if they are discolored or contain a precipitate.
474
Lucinactant
Dose
Respiratory Distress Syndrome; Prophylaxis

5.8 mL/kg birth weight intratracheally in 4 equal aliquots (with infant repositioned between
each aliquot). Up to 4 doses may be given in the first 48 hours of life. Give no more
frequently than every 6 hours[1] to 12 hours, unless surfactant is being inactivated by an
infectious process, meconium, or blood [2]. Administer prophylactic lucinactant after initial
resuscitation but within 10 to 30 minutes after birth [2][3][4].
Uses
Prevention of respiratory distress syndrome (RDS) in premature infants: Routine

continuous positive airway pressure (CPAP) is considered superior to prophylactic surfactant
therapy. It is strongly recommended that CPAP immediately after birth with subsequent
selective surfactant administration be considered as an alternative to routine intubation with
prophylactic or early surfactant administration in preterm infants [2].
Lucinactant reduced the occurrence of RDS among premature neonates (32 weeks
gestational age or younger) at high risk for developing RDS more effectively than colfosceril
palmitate (47.2% vs 39.1%; p=0.005) and also reduced the number of RDS-related deaths
compared with colfosceril palmitate and beractant treatment groups (4.7% vs 9.4%
(p=0.002) vs 10.5% (p=0.001), respectively) in a multicenter, randomized comparison trial
(n=1294) [4]. Lucinactant and poractant alfa were similar in terms of efficacy in premature
infants (24 to 28 weeks gestation) at high risk for developing RDS in a multicenter
randomized noninferiority trial (n=252). The rate of survival without BPD at 28 days (primary
outcome) was 37.8% vs 33.1%, respectively [3]. In a one-year follow-up of these 2 studies
(n=1546), lucinactant had similar efficacy to the animal-derived and synthetic exogenous
surfactant products for decreasing mortality and morbidity rates in premature neonates at
risk for RDS. Neurologic function was similar in infants who received lucinactant and those
that received other surfactants [5].
Meconium aspiration syndrome: Infants (gestational age, 35 weeks or more) treated

with lucinactant lavage within 72 hours of birth, compared with no lavage, experienced more
rapid and more sustained improvement in oxygenation and shorter ventilation times (median
4.6 vs 7.6 days); however, these outcomes were not statistically significant in an open-label,
randomized trial (n=22). Lucinactant (2.5 mg/mL) 8 mL/kg per lung was instilled over
approximately 20 seconds followed by suctioning after 5 ventilator breaths. This was
repeated followed by a third treatment of lucinactant (10 mg/mL) 8 mL/kg per lung and
suctioned at the discretion of the physician [6].

Lucinactant intratracheal suspension is indicated for the prevention of respiratory distress
syndrome (RDS) in premature infants at high risk for RDS [1].
475
Administration
Preparation
Prior to administration, warm the lucinactant intratracheal suspension vial for 15 minutes in a
preheated dry block heater set at 44 degrees C (111 degrees F). Remove the vial from the
heater and shake vigorously until the suspension is uniform and free-flowing. After
withdrawn into a syringe for administration, the temperature of the suspension will be about
37 degrees C (99 degrees F). Warmed vials should not be refrigerated after warming but
may be stored in the carton at room temperature for no more than 2 hours [1].
Administration
For intratracheal administration only. Using a 16- or 18-gauge needle, slowly draw up the
dose of warmed and vigorously shaken lucinactant intratracheal suspension into an
appropriately sized syringe [1].
Before administration of the suspension, ensure patency and proper placement of the
endotracheal tube. The endotracheal tube may be suctioned before lucinactant
administration if necessary. Allow the infant to stabilize before administration [1].
The infant should be positioned in the right lateral decubitus position with head and thorax at
a 30 degree upward inclined position. A 5-French end-hole catheter with the syringe of
lucinactant attached should be threaded through a Bodai valve (or equivalent device) to
allow maintenance of positive end-expiratory pressure. The tip of the catheter should be
advanced into the endotracheal tube and positioned so that it is slightly distal to the end of
the endotracheal tube [1].
The lucinactant dose should be delivered in 4 equal aliquots (each aliquot equal to one-fourth
of the total dose). Administer the first aliquot while continuing positive pressure mechanical
ventilation and maintaining a positive end-expiratory pressure of 4 to 5 cm Hg2O. Adjust
ventilator settings as necessary to maintain appropriate oxygenation and ventilation until the
infant is stable (oxygen saturation of at least 90% and heart rate greater than 120
beats/minute) [1].
Maintain adequate positive pressure ventilation, move the infant to the left decubitus
position, and repeat the administration procedure for the second aliquot. Pause between
administration of each aliquot to evaluate the infant's respiratory status. Move the infant to
the right decubitus position for administration of the third aliquot, and to the left decubitus
position for administration of the fourth aliquot [1].
Remove the catheter after administration of the fourth aliquot, and resume usual ventilator
management. Keep the head of the infant's bed elevated at least 10 degrees for at least 1 to
2 hours. Unless the infant develops significant airway obstruction, do not suction the infant
for the first hour after dosing [1].
MEDICATION SAFETY
Bradycardia, hypoxemia, airway obstruction, and reflux of drug into the endotracheal tube
(ETT) may occur; if reactions occur, interrupt treatment until resolved. Suctioning of the ETT
or reintubation may be necessary for persistent airway obstruction. Respiratory status may
change rapidly with administration; monitoring recommended, oxygen and ventilatory
support modifications may be required [1].
476
Adverse Effects
Bradycardia, hypoxemia, airway obstruction, and reflux of drug into the endotracheal tube
are common adverse events. In clinical trials, rates of bradycardia and oxygen desaturation
have ranged from 3% to 23% and 8% to 58%, respectively. Endotracheal tube reflux
occurred at an incidence of 18% to 27% [1][7]. The incidence of pulmonary hemorrhage,
pulmonary leaks, patent ductus arteriosus, sepsis, intraventricular hemorrhage, necrotizing
enterocolitis (grade 2 or higher), retinopathy of prematurity (grade 3 or 4), and
periventricular leukomalacia was not significantly different between lucinactant and the
comparators in clinical trials [4][3].
Gagging (20%) and coughing (27%) occurred in infants (gestational age, 35 weeks or more)
treated with lucinactant lavage within 72 hours of birth. Oxygen desaturation, probably
related to lavage therapy, occurred in 1 infant with herpes simplex virus infection [6].
Monitoring
Monitor oxygen saturation and ventilatory support frequently and modify according to
changes in respiratory status [1].
Pharmacology
Lucinactant is a synthetic, non-pyrogenic pulmonary surfactant which acts like endogenous

surfactant by restoring surface activity to the lung of premature infants deficient in
pulmonary surfactant. It consists of phospholipids, a fatty acid, and sinapultide (21-amino
acid synthetic peptide). No pharmacokinetic data are available regarding the absorption,
distribution, metabolism, or elimination of lucinactant [1].
ABOUT
Available as an intratracheal suspension containing 8.5 mL in a glass vial. Each mL contains

30 mg phospholipids (22.50 mg dipalmitoylphosphatidylcholine and 7.50 mg palmitoyloleoyl-
phosphatidylglycerol, sodium salt), 4.05 mg palmitic acid, and 0.862 mg sinapultide. Contains
no preservatives; single-use vials only. Store in refrigerator and protect from light; do not
freeze [1].
Prior to administration, warm the lucinactant intratracheal suspension vial for 15 minutes in a
preheated dry block heater set at 44 degrees C (111 degrees F). Remove the vial from the
heater and shake vigorously until the suspension is uniform and free-flowing. After
withdrawn into a syringe for administration, the temperature of the suspension will be about
477
37 degrees C (99 degrees F). Warmed vials should not be refrigerated after warming but
may be stored in the carton at room temperature for no more than 2 hours [1].
478
Magnesium sulfate
Dose
Resuscitation (Pulseless Torsades)

25 to 50 mg/kg IV/intraosseous rapid infusion (over several minutes) [1][2][3].
Hypomagnesemia
25 to 50 mg/kg IV infusion over 30 to 60 minutes; repeat dose as necessary [1][4][2]. For
hypomagnesemia/torsades with pulses, an infusion time of 10 to 20 minutes is recommended
[2].
Daily Maintenance Requirements (Parenteral Nutrition)

0.25 to 0.5 mEq/kg/day IV [5][6].
Uses
Treatment of torsades de pointes (polymorphic ventricular tachycardia associated with

long QT interval) [1][2][8]. The American Heart Association (AHA) did not review the use of
magnesium in the 2015 Neonatal Resuscitation guidelines; therefore, the 2010 AHA
guidelines still apply [9]
Treatment and prevention of hypomagnesemia[7][2][6].
Administration
Must be diluted prior to IV administration to a concentration of 100 to 200 mg/mL. Give by

rapid infusion (over several minutes) for pulseless torsades, over 10 to 20 minutes for
hypomagnesemia/torsades with pulses, and over 30 to 60 minutes for hypomagnesemia [7]
[2].
MEDICATION SAFETY
Contraindicated in patients with heart block or myocardial damage. Hypotension and

bradycardia may occur with rapid infusion. Calcium chloride should be available to reverse
magnesium toxicity. Use with caution in patients with renal impairment since magnesium
sulfate is eliminated renally. Respiratory depression may occur from high magnesium levels.
Contains aluminum which may be toxic, especially in premature neonates and patients with
https://www.micromedexsolutions.com/micromedex2/librarian/CS/FDABBA/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDS… 1/3
479
renal impairment [7].
Adverse Effects
Flushing, sweating, hypothermia, and stupor may occur [7].

Low calcium levels or bone problems, including osteopenia or fractures, may occur in
developing baby or fetus following prolonged use (greater than 5 to 7 days) of magnesium
sulfate for stopping pre-term labor in pregnant mothers [11].
D5W, NS, and LR
Solution Incompatibility
Fat emulsion.
Acyclovir, amikacin, ampicillin, aztreonam, cefazolin, cefotaxime, cefoxitin, chloramphenicol,

clindamycin, dobutamine, enalaprilat, erythromycin lactobionate, esmolol, famotidine,
gentamicin, heparin sodium, hydrocortisone sodium succinate, insulin, linezolid, meropenem,
metoclopramide, metronidazole, micafungin, milrinone, morphine, nafcillin, nicardipine,
ondansetron, oxacillin, penicillin G potassium, piperacillin, piperacillin/tazobactam, potassium
chloride, propofol, sodium nitroprusside, tobramycin, trimethoprim/sulfamethoxazole, and
vancomycin.
Amiodarone, amphotericin B, calcium chloride, cefepime, pantoprazole, and sodium

bicarbonate.
Monitoring
Monitor serum and urinary magnesium levels [10][7]. Assess other electrolytes (calcium,
potassium, phosphorus) and renal function periodically.
480
Pharmacology
Magnesium is a cation of the intracellular fluid that is necessary for the activity of many
enzyme systems and plays an important role in neurochemical transmission and muscular
excitability. Approximately 99% of total body magnesium is in the intracellular compartment
(bone, 85%; soft tissue and liver, 14%) and only 1% is present in the extracellular fluid.
Because of this, serum concentrations do not adequately reflect total body magnesium
stores. Most of the filtered magnesium (95%) is reabsorbed by the kidney. Magnesium
deficiency leads to varied structural and functional abnormalities [10][7].
Signs of hypomagnesemia include tetany, cardiac arrhythmia, decreased bone stability,
apathy, and increased susceptibility to epileptic seizures. Magnesium deficiency is associated
with hypocalcemia, hypokalemia, hypophosphatemia, decreased urinary magnesium and
calcium levels, and decreased magnesium levels in cerebrospinal fluid, bone, muscle, and
hematopoietic cells [12][13].
ABOUT
Supplied as 50% concentration in 2-, 10-, and 50-mL single dose vials containing 500 mg/mL
of magnesium sulfate which provides 4.06 mEq each of magnesium and sulfate. Osmolarity is
4.06 mOsm/mL; pH range of 5.5 to 7 [7][14].
481
Mannitol
Dose
Prior to use, evaluate renal, cardiac, and pulmonary status of the patient and correct fluid
and electrolyte imbalances, especially in patients with renal dysfunction [1].
Preterm and term neonates may be at higher risk for fluid and electrolyte abnormalities
following mannitol administration due to decreased glomerular filtration rate and limited
ability to concentrate urine [1].
The total dosage, concentration, and rate of administration depend on the age, weight, and
condition of the patient being treated, including fluid requirement, electrolyte balance, serum
osmolality, urinary output, and concomitant therapy [1].
Elevated Intracranial Pressure
0.25 g/kg IV over 30 minutes; may repeat every 6 to 8 hours [1].
Monitor during and following infusion and discontinue if renal, cardiac, or pulmonary status
worsens or CNS toxicity develops [1].
Elevated Intraocular Pressure

1.5 to 2 g/kg of a 20% w/v solution (7.5 to 10 mL/kg) or as a 15% w/v solution (10 to 13
mL/kg) as a single dose IV over at least 30 minutes; when used preoperatively, administer
60 to 90 minutes prior to surgery [1].
Uses

Intravenous
•Reduction of intracranial pressure and treatment of cerebral edema [1].
•Reduction of high intraocular pressure [1]
Administration
Injection:
•For IV infusion, preferably into a central vein [1].
•Do not administer simultaneously with blood products through the same administration set
because of the possibility of pseudoagglutination or hemolysis [1].
•Use administration sets with a final in-line filter because of potential for crystals to form [1].
•Use a non-vented infusion set or close the vent on a vented set, avoid multiple connections,
and do not connect flexible containers in series to prevent air embolism [2]
•Fully evacuate residual gas in the container prior to administration and do not pressurize the
flexible container to increase flow rates to prevent air embolism [2]
•If administration is controlled by a pumping device, turn off pump before the container runs
https://www.micromedexsolutions.com/micromedex2/librarian/CS/E1EFDD/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDS… 1/4
482
dry to prevent air embolism [2]
•For single use only. Discard unused portion [1].
MEDICATION SAFETY
Contraindications
IV formulation [1]
Anuria
Severe hypovolemia
Active intracranial bleeding, except during craniotomy
Preexisting severe pulmonary vascular congestion or pulmonary edema
Precautions
Intravenous
Administration: Peripheral venous irritation, including phlebitis, can occur when
concentrations of 10% or greater are used [1]
Administration: Severe infusion site reactions (eg, compartment syndrome and swelling
associated with extravasation) can occur [1]
Cardiovascular: Hypervolemia may occur and can lead to or exacerbate existing congestive
heart failure; increased risk with accumulation of mannitol due to insufficient renal excretion
[1]
Cardiovascular: Osmotic diuresis due to mannitol may cause or worsen
dehydration/hypovolemia and hemoconcentration; hyperosmolarity may also occur [1]
Cardiovascular: Fluid and electrolyte imbalance (eg, hypernatremia, hyponatremia,
hypokalemia, hyperkalemia, and metabolic acidosis/alkalosis), including severe and
potentially fatal imbalances, may occur; increased risk in pediatric patients younger than 2
years, particularly preterm and term neonates; monitoring recommended and discontinuation
may be required [1]
Concomitant use: with neurotoxic and nephrotoxic drugs (eg, aminoglycosides) or other
diuretics should be avoided, if possible [1]
Endocrine and metabolic: Hyponatremia, new-onset or exacerbation, may occur [1]
Immunologic: Serious hypersensitivity reactions, including anaphylaxis, hypotension, and
dyspnea resulting in cardiac arrest and death, have been reported with mannitol injection; if
hypersensitivity reaction occurs, stop infusion immediately [2]
Neurological: CNS toxicity (eg, confusion, lethargy, coma) has been reported with some
cases resulting in fatalities; monitoring recommended and discontinuation of therapy may be
necessary [1]
Neurologic: At high concentrations, mannitol may cross the blood brain barrier and
interfere with the ability of the brain to maintain the pH of the cerebrospinal fluid especially
in the presence of acidosis [1]
Neurologic: Preexisting compromise of the blood brain barrier; increased risk of increasing
cerebral edema (general and focal) associated with repeated or continued use [1]
Neurologic: Rebound increase in intracranial pressure may occur several hours after
infusion; increased risk in patients with compromised blood brain barrier [1]
Renal: Renal complications, including irreversible renal failure, have been reported;
discontinuation may be required [2]
483
Renal: Reversible, oliguric acute kidney injury (AKI) has occurred in patients with normal
renal function who received large IV doses; patients with oliguric AKI who develop anuria
during therapy have increased risk of congestive heart failure, pulmonary edema,
hypertensive crisis, coma, and death; monitor during and following administration;
discontinuation may be required [2]
Renal: Osmotic nephrosis can occur with potential to lead to chronic or end-stage renal
failure; increased risk with preexisting renal disease or concomitant use of nephrotoxic
agents and other diuretics; monitoring recommended [1]
Renal: Urine output, inadequate; during infusion could lead to water intoxication or
congestive heart failure; monitoring recommended and infusion suspension may be
necessary [1]
Adverse Effects
Common: Hypersensitivity reactions, renal failure, CNS toxicity, hypo/hypervolemia,

hypo/hypernatremia, hypo/hyperkalemia, and infusion site reactions [1].
Monitoring
Intravenous:[2]
•Monitor for hypersensitivity reactions during and following infusion, including laboratory
tests for changes in fluid and electrolyte status [1].
•Closely monitor renal function, especially in patients with renal disease, conditions that put
them at high risk for renal failure, or those receiving potentially nephrotoxic drugs or other
diuretics [1].
Monitor during and after reduction of Intracranial pressure:
Serum osmolarity
Fluid and serum electrolytes, including sodium, potassium, calcium, and phosphate
Acid base balance
Osmol gap
Signs of hypovolemia and hypervolemia, including urine output
Renal function
Cardiac function
Pulmonary function
Intracranial pressure
Pharmacology
484
Intravenous mannitol is confined to the extracellular space and rapidly excreted by the
kidney. Three hours after administration, approximately 80% of a 100-g dose is recovered in
the urine. Mannitol is not secreted by tubular cells; it is freely filtered by the glomeruli, with
less than 10% tubular reabsorption. Glomerular filtrate osmolarity elevation, and resulting
interference with tubular reabsorption of water, induces diuresis. Sodium and chloride
excretion is also increased by this process [3].
ABOUT
Intravenous: 5%, 10%, 15%, and 20% solution in flexible containers, and 25% flip-top 50-
mL vial (all single-dose) [1][3].
Admixing with other medications is not recommended [1].
Inspect for crystals prior to use; if crystals are visible re-dissolve by warming solution up to
70 degrees C, with agitation. Do not heat in water or a microwave oven due to potential for
product contamination or damage. Allow solution to cool to room or body temperature before
reinspection for crystals and use [1].
Dissolve crystals in the flip-top vial by warming bottle in hot water at 80 degrees C;
periodically shake vigorously. The 25% concentration may be autoclaved at 121 degrees C
for 20 minutes at 15 psi. Do not place 25% mannitol injection in polyvinylchloride bags; a
white flocculent precipitate may form from contact with PVC surfaces [3].
485
MCT Oil
Dose
Medium Chain Triglyceride Oil
Medium chain triglycerides (MCT) are lipid fractions of coconut oil consisting of triglycerides
with chain lengths of 6 to 10 carbons. Used to supplement orally, or added to tube feeding
formulas. Mixes easily with enteral formulas.
Pharmacology
Osmolality (mOsm/kg water): Not Available
Supplied: 1 quart glass bottles.
Ingredients: Medium chain triglycerides.
MCT Oil
per 15 mL per 89 mL
Nutrient per mL
(1 tbsp) (3 fl oz)
Calories 7.7 115 685.3
Protein, g 0 0 0
Fat, g 0.94 14 44.5
Carbohydrate, g 0 0 0
Water, g 0 0 0
Linoleic Acid, g 0.367 5.5 32.63
Fatty Acid Distribution

Shorter than carbon 8 <6%
Caprylic C8:0 67%
Capric C10:0 23%
Longer than C10:0 <4%
ABOUT
https://www.micromedexsolutions.com/micromedex2/librarian/CS/C1213D/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/2
486
For oral use only. Do not give parenterally (IV). Use within 60 to 90 days after a bottle is
opened. Do not store in plastic container. MCT may break or soften plastic containers.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/C1213D/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 2/2
487
Meropenem
Dose
Anthrax; meningitis or disseminated infection and meningitis cannot be ruled out

(as part of a triple therapy regimen) [1]
32 weeks gestational age to full-term
0 to 1 week: 20 mg/kg/dose IV every 8 hours
1 to 4 weeks : 30 mg/kg/dose IV every 8 hours
Duration: 2 to 3 weeks or more until stable. Continue antimicrobial course of prophylaxis
(usually oral therapy) for up to 60 days from onset of illness [1].
Anthrax; meningitis ruled out (as part of a combination regimen) [1]

32 to 34 weeks gestational age
1 to 4 weeks: 20 mg/kg/dose IV every 8 hours
34 weeks gestational age or older
Intra-abdominal and non-CNS infections

Less than 32 weeks GA and less than 14 days PNA: 20 mg/kg IV every 12 hours [2][3]
[4].
Less than 32 weeks GA and 14 days PNA and older: 20 mg/kg IV every 8 hours [2][3]
[4].
32 weeks GA and older, and less than 14 days PNA: 20 mg/kg IV every 8 hours [2][3]
[4].
32 weeks GA and older, and 14 days PNA and older: 30 mg/kg IV every 8 hours [2][3]
[4].
Consider concomitant use of an aminoglycoside antibiotic [3].
Meningitis, Bacterial
Data regarding appropriate dosing for CNS infections are lacking [4]. Consider 40
mg/kg/dose at the recommended age-specific dosing interval [5][6]
Less than 32 weeks GA and less than 14 days PNA: every 12 hours [4].
Less than 32 weeks GA and 14 days PNA and older: every 8 hours [4].
32 weeks GA and older: every 8 hours [4].
Uses
Anthrax[1]:

https://www.micromedexsolutions.com/micromedex2/librarian/CS/1D9F0E/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/5
488
Plus
Preferred: Clindamycin. Alternatives in order of preference: linezolid, doxycycline (not
ruled out) (IV)
Triple IV Therapy
moxifloxacin
Plus
(alternative).
Plus
Intra-abdominal infections, suspected or complicated [3], or other serious infections
caused by susceptible Gram-negative organisms resistant to other antibiotics [15][16][17].
May be useful in treating neonates with meningitis, however, data are lacking.

Complicated skin/skin structure infections due to Staphylococcus aureus (methicillin-
Streptococcus pyogenes S agalactiae
susceptible isolates only), , , viridans group streptococci,
Enterococcus faecalis Pseudomonas aeruginosa
(vancomycin-susceptible isolates only), ,
Escherichia coli Proteus mirabilis Bacteroides fragilis Peptostreptococcus
, , , and species in
pediatric patients 3 months and older [7].
Intra-abdominal infections [18] including complicated appendicitis and peritonitis caused by
viridans group streptococci, E coli Klebsiella pneumoniae P aeruginosa B fragilis B
, , , ,
thetaiotaomicron , and Peptostreptococcus
species in pediatric patients 3 months and older
[7]. Meropenem is considered an appropriate single agent for pediatric patients with a
complicated extra-biliary intra-abdominal infection [18]
Bacterial meningitis caused by S pneumoniae (penicillin-susceptible isolates), Haemophilus
influenzae , and Neisseria meningitidis
in pediatric patients 3 months and older [7].
Administration
Administer as an IV infusion over 30 minutes [4] at a concentration of 1 to 20 mg/mL [7] .

Recommended standard concentrations are 20 and 50 mg/mL [8].
Prolonged Infusion: There are some data that promote prolonged infusions (e.g. over 4
hours) [9] particularly for resistant organisms in neonates [10]. In contrast, infusions of 20
mg/kg over 30 minutes were demonstrated pharmacokinetically to be adequate for very low
birth weight infants [11]. Stability of meropenem needs to be considered as it is dependent
on diluent, concentration, and temperature [7]. Some studies demonstrated longer stability
times [12][13][14].
489
MEDICATION SAFETY
Contraindications
Contraindicated in patients with known hypersensitivity to carbapenems or previous
anaphylactic reactions to beta-lactams. Serious and occasionally fatal hypersensitivity
(anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams;
these reactions are more likely to occur in those with a history of hypersensitivity to other
beta-lactams or to multiple allergens. Before initiating therapy, obtain a detailed history of
previous hypersensitivity reactions [19].
Precautions
Concomitant use: Coadministration with valproic acid or divalproex sodium is generally not
recommended due to a reduction in valproic acid concentrations that may not respond to a
dose increase. In patients with well-controlled seizures on valproic acid or divalproex sodium,
antibiotics other than carbapenems are recommended, and if coadministration of meropenem
is necessary, supplemental anticonvulsant therapy is recommended [19]
Dermatologic: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome,
toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, erythema
multiforme, and acute generalized exanthematous pustulosis have been reported; if signs
and symptoms appear, immediately withdraw therapy and consider an alternative [20].
Neurological:Seizures and other CNS adverse events have been reported with meropenem
therapy; these occurred mainly in patients with CNS disorders (eg, brain lesions or history of
seizures) or patients with bacterial meningitis and/or compromised renal function [19].
Adverse Effects
Diarrhea (4%), nausea/vomiting (1%) and rash (2%). May cause inflammation at the
injection site. The use of carbapenem antibiotics can result in the development of
cephalosporin resistance in Enterobacter Pseudomonas Serratia Proteus Citrobacter
, , , , , and
Acinetobacter species. The risks of pseudomembranous colitis and fungal infections are also
increased.
D5W, D10W, and NS.
490
Aminophylline, atropine, caspofungin, cimetidine, dexamethasone, digoxin, dobutamine,
dopamine, enalaprilat, fluconazole, furosemide, gentamicin, heparin, insulin, linezolid,
metoclopramide, milrinone, morphine, norepinephrine, phenobarbital, potassium chloride,
ranitidine, and vancomycin.
Acyclovir, amphotericin B, calcium gluconate, metronidazole, sodium bicarbonate, and

zidovudine.
Monitoring
Periodic CBC (for thrombocytosis and eosinophilia) and hepatic transaminases. Assess IV site
for signs of inflammation.
Pharmacology
Mechanism of action: Meropenem is a broad-spectrum carbapenem antibiotic that

penetrates well into the CSF and most body tissues. It exhibits time-dependent killing of
gram-negative and gram-positive pathogens, and the goal of therapy is to keep free drug
concentrations above the MIC for at least 40% of the dosing interval. It is relatively stable to
inactivation by human renal dehydropeptidase. [21].
Protein binding: Plasma protein binding is minimal.

Clearance: Directly related to renal function, and 70% of a dose is recovered intact in the
urine. Measured renal clearance and the effect of probenecid demonstrate that both
glomerular filtration and tubular secretion are involved in renal elimination.
Metabolism: Hepatic function does not affect pharmacokinetics [21].
Pharmacokinetic parameters in patients less than 3 months of age following treatment with
combination antibacterial drug therapy: [2]
Pharmacokinetic Parameters
GA: less than 32 GA: less than 32 GA: 32 weeks or GA: 32 weeks or
weeks and PNA: weeks and PNA: 2 older and PNA: less older and PNA: 2
Parameters less than 2 weeks weeks or older (20 than 2 weeks (20 weeks or older (30 Overall
(20 mg/kg every 12 mg/kg every 8 mg/kg every 8 mg/kg every 8
hours) hours) hours) hours)
CL
0.089 0.122 0.135 0.202 0.119
(L/hr/kg)
V (L/kg) 0.489 0.467 0.463 0.451 0.468
AUC (mcg-
448 491 445 444 467
hr/mL)
Cmax 44.3 46.5 44.9 61 46.9
491
(mcg/mL)
Cmin
5.36 6.65 4.84 2.1 5.65
(mcg/mL)
T1/2 (hr) 3.82 2.68 2.33 1.58 2.68
Values were obtained from a population pharmacokinetic analysis of sparse data
GA: gestational age; PNA: postnatal age
Merrem IV product information, 2014; AUC is from 0 to 24
ABOUT
Availability: Powder for injection in 500-mg, and 1000-mg vials.

Dilution and Stability
IV Bolus: 10 mL of compatible diluent (500-mg vial) or 20 mL (1000-mg vial) for IV bolus.
When reconstituted with sterile water for injection up to 50 mg/mL, stable for up to 3 hours
at room temperature or up to 13 hours when refrigerated (at or up to 5 degrees C) [7].
IV Infusion: Concentrations from 1 to 20 mg/mL, in NS, are stable for 1 hour at or up to 25
degrees C or 15 hours at or up to 5 degrees C. Concentrations from 1 to 20 mg/mL, in D5W,
should be used immediately [7].
Some studies demonstrated longer stability times [12][13][14]
492
Methadone
Dose
Neonatal Abstinence Syndrome

Initial dose: 0.05 to 0.1 mg/kg per dose orally every 6 to 24 hours [1][2][3][4][5]. Adjust
dose (in 10% to 20% increments) and weaning schedule based on signs and symptoms of
withdrawal [2][4].
Weaning Protocol[6]
Gestational age, 34 weeks or more
Start at step 1 for infants with 3 consecutive Finnegan scores 8 or more or 2 consecutive
Finnegan scores 12 or more:
Step 1: 0.1 mg/kg orally every 6 hours for 4 doses
Step 8: 0.01 mg/kg orally every 24 hours for 1 dose
Weaning
Wean to the next step if the average Finnegan score is less than 8 for the past 24 hours
If the average Finnegan score is 8 to 12, do not wean
If the average Finnegan score is at least 12, consider an extra dose of methadone at
the current step, or return to previous step
Escalation
If the infant fails step 1 (score of greater than 12), consider steps 1A through 1C
Step 1A: 0.1 mg/kg orally every 4 hours for 6 doses
Step 1B: 0.1 mg/kg orally every 8 hours for 3 doses
Step 1C: 0.1 mg/kg orally every 12 hours for 2 doses
Adjunct:
Consider adding phenobarbital if unable to wean for 2 consecutive days
Discharge
Observe for 72 hours from the last dose of step 8
Dose Adjustments
Liver Impairment: Consider lower initial dose and titrate slowly [7][8][9].
Renal Impairment: Consider lower initial dose with longer dosing interval and titrate slowly
493
[7][8][9]
Uses
Neonatal abstinence syndrome (NAS)[1][2].

Sublingual buprenorphine was associated with the largest reduction in length of treatment
and length of stay for NAS in a network meta-analysis of 18 randomized controlled trials
(n=1072) of buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted
tincture of opium, morphine, methadone, and phenobarbital. Morphine was the least
effective opioid [10]. The findings should be interpreted with caution due to significant study
limitations [10][11]
Compared with morphine: Methadone outperformed morphine for the treatment of NAS
in a multicenter, randomized, double-blind study of 116 term infants (median LOS (16 vs 20
days, p=0.005), LOS attributable to NAS (16 vs 19 days, p=0.005), and length of drug
treatment (11.5 vs 15 days, p=0.009)). Initial oral doses were 0.3 mg/kg/day for Finnegan
score (FS) of 8 to 10, 0.5 mg/kg/day for FS of 11 to 13, 0.7 mg/kg/day for FS 14 to 16, and
0.9 mg/kg/day for FS of 17 or more. The total daily doses were divided every 4 hours for
morphine and every 8 hours for methadone. A nonalcoholic solution of methadone was
compounded [12].
Neonatal abstinence syndrome was treated for a median of 14 days with methadone
compared with 21 days for morphine (p=0.008) in a double-blind, randomized trial (n=78).
All neonates were 35 weeks gestational or more and prenatal exposure was either
methadone or buprenorphine [13].
Compared with buprenorphine: A shorter duration of opioid treatment (9.4 vs 14 days)
and shorter length of inpatient stay (16.3 vs 20.7 days) with a sublingual buprenorphine
protocol compared with oral methadone protocol was demonstrated in a retrospective
analysis of 201 infants (34 weeks' gestation or older) with NAS. Infants exposed in utero to
methadone were excluded [14].
MEDICATION SAFETY
Contraindications
•Significant respiratory depression, in the absence of resuscitative equipment or in
unmonitored settings [19][8][9]
•Acute or severe bronchial asthma in an unmonitored setting or in the absence of
resuscitative equipment [19][8][9]
•Known or suspected paralytic ileus [19][8][9]
•Known or suspected gastrointestinal obstruction [19][8][9]
Precautions
Administration: Crushing, chewing, or dissolving may result in uncontrolled delivery and
increased risk of overdose or death [20]
Administration: The manufacturer recommends that methadone not be used as an as-
needed (prn) analgesic [20]
Cardiovascular: Severe hypotension, orthostatic hypotension, and syncope have been
reported [19][9][8][21]; increased risk in those with reduced blood volume or who use CNS
494
depressants concomitantly; monitoring recommended [19]
Cardiovascular: Avoid use in patients with circulatory shock [19].
Concomitant use: Avoid concomitant use with mixed agonist/antagonist or partial agonists
[20][9][8]
Endocrine and metabolic: Opioids may rarely lead to adrenal insufficiency due to
inadequate amounts of cortisol. If adrenal insufficiency is suspected, perform diagnostic
testing, treat with corticosteroids if confirmed, wean patient off of opioid if appropriate, and
continue to assess adrenal function [22].
Endocrine and metabolic: Preexisting hypothyroidism increases the risk for respiratory
depression; reduced initial dose recommended [23]
Gastrointestinal: Gastrointestinal obstruction; avoid use [9][8]
Hepatic: Spasm of sphincter of Oddi, and worsen biliary tract disease, including acute
pancreatitis may occur; monitoring recommended [19][9][8]
Hepatic: Hepatic disease may increase risk of toxicity and CNS depressant effects; use lower
initial dose and titrate slowly; monitoring recommended [9][8]
Neurologic: Potentially life-threatening serotonin syndrome has been reported; the risk is
increased with concomitant use of serotonergic drugs [22]
Neurologic: Seizure disorders may be induced or aggravated; monitoring recommended
[20][9][8]
Neurologic: Severe sedation, coma, and death have been reported [9][8]
Neurologic: Avoid use in patients with impaired consciousness or coma [20]
Neurologic: Use in patients at risk or who have increased intracranial pressure (eg, brain
tumors, head injury, intracranial lesions) may exaggerate respiratory depression and sedation
and further increase intracranial pressure; opioids may obscure clinical course of head injury;
monitoring recommended [20][9][8]
Prolonged use: Long-term use of opioids may be associated with decreased sex hormone
levels and symptoms such as reduced interest in sex, impotence, or infertility. Laboratory
evaluation may be warranted [22].
Renal: Renal disease may increase risk of CNS depressant effects; use lower initial dose and
titrate slowly; monitoring recommended [9][8]
Respiratory: Respiratory depression is more likely to occur in cachectic or debilitated
patients; monitoring recommended [20][9][8]; reduced initial dose recommended [9][8]
Respiratory: Use in patients with preexisting chronic pulmonary disease (eg, COPD, cor
pulmonale, asthma) may further decrease respiratory drive leading to apnea, even at
therapeutic doses; monitoring recommended and consider nonopioid alternatives if feasible
[20][9][8]
Respiratory: Increased risk of decreased respiratory drive, including apnea, in patients with
a decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory; monitoring
recommended, especially during initiation, dose increases, and concomitant use with other
drugs associated with respiratory depression. Alternative therapy may be required [19].
Respiratory: Sleep-related breathing disorders including central sleep apnea and sleep-
related hypoxemia may occur and risk increases in a dose-dependent fashion; dose reduction
may be necessary [24].
Respiratory: Peak respiratory depressant effect occurs later and persists longer than
analgesic effect, which may result in overdose [9][8]
Withdrawal: Severe withdrawal symptoms may occur with abrupt discontinuation [20][9]
[8] or if a mixed agonist/antagonist or partial opioid agonist is administered with or after full
opioid agonist therapy [20]
Adverse Effects
495
Respiratory depression in excessive doses. Ileus and delayed gastric emptying. In a single
case report, QTc prolongation was noted in a term infant born to a mother receiving
methadone maintenance therapy (50 mg/day). After birth, the infant's resting HR was 80 to
90 beats per minute and ECG showed a QTc of 510 msec. This resolved spontaneously over
5 days [16].
Black Box Warning
Warning: Addiction, Abuse And Misuse; Life-Threatening Respiratory Depression; Accidental

Ingestion; Life-Threatening QT Prolongation; Neonatal Opioid Withdrawal Syndrome;
Interactions With Drugs Affecting Cytochrome P450 Isoenzymes; Risks From Concomitant
Use With Benzodiazepines Or Other CNS Depressants; And Treatment For Opioid Addiction
[18]
Addiction, Abuse, and Misuse
Methadone hydrochloride tablets expose patients and other users to the risks of opioid
addiction, abuse, and misuse, which can lead to overdose and death. Assess each
patient’s risk prior to prescribing methadone hydrochloride tablets, and monitor all
patients regularly for the development of these behaviors and conditions
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of
methadone hydrochloride tablets. The peak respiratory depressant effect of methadone
occurs later, and persists longer than the peak analgesic effect, especially during the
initial dosing period or following a dose increase. Monitor for respiratory depression,
especially during initiation of methadone hydrochloride tablets or following a dose
increase
Accidental Ingestion
Accidental ingestion of even one dose of methadone hydrochloride tablets, especially by
children, can result in a fatal overdose of methadone
Life-Threatening QT Prolongation
QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred
during treatment with methadone. Most cases involve patients being treated for pain
with large, multiple daily doses of methadone, although cases have been reported in
patients receiving doses commonly used for maintenance treatment of opioid addiction.
Closely monitor patients with risk factors for development of prolonged QT interval, a
history of cardiac conduction abnormalities, and those taking medications affecting
cardiac conduction for changes in cardiac rhythm during initiation and titration of
methadone hydrochloride tablets
Neonatal Opioid Withdrawal Syndrome
Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of
use of methadone hydrochloride tablets during pregnancy. NOWS may be life-
threatening if not recognized and treated in the neonate. The balance between the risks
of NOWS and the benefits of maternal methadone hydrochloride use may differ based
on the risks associated with the mother’s underlying condition, pain, or addiction.
Advise the patient of the risk of NOWS so that appropriate planning for management of
the neonate can occur.
Cytochrome P450 Interaction
The concomitant use of methadone hydrochloride tablets with all cytochrome P450 3A4,
2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma
concentrations, which could cause potentially fatal respiratory depression. In addition,
discontinuation of concomitantly used cytochrome P450 3A4, 2B6, 2C19, or 2C9
496
inducers may also result in an increase in methadone plasma concentration. Follow
patients closely for respiratory depression and sedation, and consider dosage reduction
with any changes of concomitant medications that can result in an increase in
methadone levels
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS)
depressants, including alcohol, may result in profound sedation, respiratory depression,
coma, and death.
Reserve concomitant prescribing of methadone benzodiazepines or other CNS
depressants for use in patients in methadone treatment for whom alternative treatment
options are inadequate.
Limit dosages and durations to the minimum required
Follow patients for signs and symptoms of respiratory depression and sedation. If the
patient is visibly sedated, evaluate the cause of sedation, and consider delaying or
omitting the daily methadone dose
Conditions For Distribution And Use Of Methadone Products For The Treatment Of
Opioid Addiction
For detoxification and maintenance of opioid dependence, methadone should be
administered in accordance with the treatment standards cited in 42 CFR Section 8,
including limitations on unsupervised administration
NS.
Atropine sulfate, dexamethasone, lorazepam, metoclopramide, midazolam, and

phenobarbital.
Phenytoin.
Monitoring
Monitor respiratory, central nervous system, and cardiac status closely, especially during drug
initiation and titration [7][8][9]. A 12-lead ECG should be obtained on methadone-exposed
infants experiencing bradycardia or tachycardia [15][16]. Assess for gastric residuals,
abdominal distention, and loss of bowel sounds. For infants experiencing neonatal abstinence
syndrome, monitor and score signs of drug withdrawal using a published abstinence
497
assessment tool such as the modified Neonatal Abstinence Scoring System (Finnegan) or the
Lipsitz tool [1][17].
Pharmacology
Long-acting narcotic analgesic. Oral bioavailability is 50%, with peak plasma levels obtained
in 2 to 4 hours. Metabolized extensively via hepatic N-demethylation. Highly protein bound
(90% adults). Serum half-life ranges from 16 to 25 hours in neonates and is prolonged in
patients with renal failure. Rifampin and phenytoin accelerate the metabolism of methadone
and can precipitate withdrawal symptoms.
Factors to consider which differentiate methadone from other opioids [7][8][9]:
High inter-patient variability in absorption, metabolism, and relative analgesic potency
Duration of analgesic effect shorter (based on single-dose studies) than the plasma
half-life
Steady-state plasma concentrations, and full analgesic effects, not attained until 3 or
more days after initiation of dosing
Peak respiratory depressant effect occurs later and persists longer than peak analgesic
effect
With repeated dosing, methadone is retained in the liver and slowly released, which
prolongs the duration of potential toxicity
Narrow therapeutic index, especially in combination with other drugs
High opioid tolerance does not eliminate the possibility of overdose with methadone
ABOUT
Available as oral solutions in 1- and 2-mg/mL concentrations containing 8% alcohol, and a

10-mg/mL alcohol-free solution[8][9] Also available as 5- and 10-mg tablets [7].
498
Metoclopramide
Dose
Tablets are not recommended for use in pediatric patients due to an increased risk of tardive
dyskinesia and other extrapyramidal symptoms, as well as a risk of methemoglobinemia in
neonates[1].
0.033 to 0.1 mg/kg/dose orally or IV every 8 hours.
Uses
To facilitate gastric emptying and gastrointestinal motility. May improve feeding

intolerance. Use in gastroesophageal reflux patients is controversial.
(Also used to enhance lactation--10 mg every 8 hours.)
Apnea of prematurity: Reducing gastric acidity or increasing gastric motility for the sole
purpose to reduce apnea episodes is not supported by the literature [3].
Administration
Intermittent IV infusion: Dilute to 0.2 mg/mL in D5W or NS and infuse over a minimum
of 15 minutes [2].
MEDICATION SAFETY
CONTRAINDICATIONS[1][4]
In patients when stimulation of gastrointestinal motility may be harmful (eg, presence
of gastrointestinal hemorrhage, mechanical obstruction, or perforation)
In patients with pheochromocytoma (may cause a hypertensive crisis) r other
catecholamine-releasing paragangliomas
In patients with epilepsy
In patients receiving other drugs that are likely to cause extrapyramidal reactions
In patients with a history of tardive dyskinesia or a dystonic reaction to metoclopramide
(oral)
PRECAUTIONS
https://www.micromedexsolutions.com/micromedex2/librarian/CS/5EE7F2/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
499
Cardiovascular: Catecholamine release and elevated blood pressure may occur [4]; avoid
use in patients with hypertension or those taking monoamine oxidase inhibitors [1].
Cardiovascular: Fluid retention and volume overload may occur, especially in patients with
cirrhosis or congestive heart failure [4]; discontinue if such reactions occur [1].
Endocrine and metabolic: Hyperprolactinemia may occur and lead to galactorrhea,
amenorrhea, or gynecomastia [1].
Neurologic: Neuroleptic malignant syndrome (NMS) has been reported rarely; immediately
discontinue use if occurs [4]; avoid use in patients receiving other drugs associated with
NMS, such as typical and atypical antipsychotics [1].
Neurologic: Acute dystonic reactions, which may present as stridor and dyspnea, have been
reported and usually occur during first 24 to 48 hours of therapy; risk is increased pediatric
patients and with higher doses used for prophylaxis of chemotherapy-related vomiting.
Treatment of symptoms with diphenhydramine or benztropine may be required [4]; avoid
use in patients receiving other drugs likely to cause extrapyramidal symptoms [1].
Neurologic: Tardive dyskinesia (TD), which may be irreversible, may occur; risk increased
with duration of treatment and total cumulative dose; discontinue use if signs or symptoms
develop [4]; avoid use in patients receiving other drugs likely to cause TD [1].
Neurologic: Parkinsonian-like symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like
facies) have been reported within first 6 months of use; symptoms generally resolve
following discontinuation [4]; avoid use in patients with Parkinson disease and those being
treated with antiparkinsonian drugs [1].
Neurologic: Akathisia (anxiety, agitation, jitteriness, insomnia, pacing, foot tapping) has
occurred; if symptoms resolve, consider reinitiating at a lower dosage [1].
Psychiatric: Depression has been reported in patients with and without a history of
depression; symptoms may range from mild to severe and include suicidal ideation and
suicide [4]; avoid use in patients with a history of depression [1].
Psychiatric: Anxiety and restlessness, followed by drowsiness, may occur with too rapid
administration [4].
Surgery: Additional pressure on suture lines following a gut anastomosis or closure may
occur due to promotility activity [4].
Adverse Effects
Intended for short-term use (several weeks). Dystonic reactions and extrapyramidal
symptoms are seen frequently at higher doses and with prolonged use; children are more
susceptible than adults.
Black Box Warning
Tardive Dyskinesia
Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder
that is often irreversible. The risk of developing tardive dyskinesia increases with duration of
treatment and total cumulative dose. Metoclopramide therapy should be discontinued in
patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment
for tardive dyskinesia. In some patients, symptoms may lessen or resolve after
metoclopramide treatment is stopped. Treatment with metoclopramide for longer than 12
weeks should be avoided in all but rare cases where therapeutic benefit is thought to
outweigh the risk of developing tardive dyskinesia [1][4].
500
D5W and NS.
Acyclovir, aminophylline, atropine, aztreonam, caffeine citrate, cimetidine, ciprofloxacin,

clindamycin, dexamethasone, famotidine, fentanyl, fluconazole, heparin, hydrocortisone,
lidocaine, linezolid, meropenem, methadone, midazolam, morphine, multivitamins,
piperacillin/tazobactam, potassium chloride, potassium phosphate, prostaglandin E1,
quinupristin-dalfopristin, ranitidine, remifentanil, and zidovudine.
Ampicillin, calcium gluconate, cefepime, chloramphenicol, erythromycin lactobionate,

furosemide, penicillin G, propofol, and sodium bicarbonate.
Monitoring
Measure gastric residuals. Observe for increased irritability or vomiting.
Pharmacology
Derivative of procainamide. Exact mode of action is unknown; however, metoclopramide has

both dopamine-receptor blocking activity and peripheral cholinergic effects. Well absorbed
from gastrointestinal tract. Variable first-pass metabolism by liver. Significant fraction
excreted unchanged in urine. Lipid-soluble, large volume of distribution. Serum half-life in
adults is 4 hours; prolonged in patients with renal failure.
ABOUT
501
Available as a 5-mg/mL injectable solution (osmolarity 280 mOsm/kg). Protect from light.
A dilution made with preservative-free NS is stable for 24 hours at room temperature under
normal light or for 48 hours if protected from light [2]. A 0.1 mg/mL dilution may be made by
adding 0.4 mL of the 5-mg/mL concentration to 19.6 mL of preservative-free NS.
Oral preparation available in 1-mg/mL concentration. A 0.1 mg/mL oral dilution may be made
by adding 1 mL of the 1-mg/mL concentration to 9 mL simple syrup. Stable for 4 weeks at
room temperature.
502
MetroNIDAZOLE
Dose
Anaerobic Infections
Loading Dose † ‡ ¶ Maintenance Dose

Postmenstrual Age Interval
IV or Oral ♦ IV or Oral ♦
24 to 25 weeks 15 mg/kg 7.5 mg/kg † ¶ 24 hours † ¶
26 to 27 weeks 15 mg/kg 10 mg/kg † ¶ 24 hours † ¶
28 to 33 weeks 15 mg/kg 7.5 mg/kg † ‡ 12 hours † ‡
34 to 40 weeks 15 mg/kg 7.5 mg/kg † ‡ 8 hours † ‡
Greater than 40 weeks 15 mg/kg 7.5 mg/kg † ‡ 6 hours † ‡
Postmenstrual Age = gestational age plus postnatal age
♦ Doses for IV and oral routes are the same in adults for the treatment of anaerobic infections
(Product Information metronidazole IV injection, Baxter Healthcare 2011)
† Dannelley, 2017
‡ Cohen-Wolkowiez, 2013; Cohen-Wolkowiez, 2012
¶ Suyagh, 2011
• Safety and efficacy have not been established with the above regimens [1].
• Dose simulations of the above regimens predict steady-state trough concentrations of
greater than 8 mg/L in infants with a gestational age (GA) of 28 weeks or more [2][3] and
steady-state concentrations of greater than 6 mg/L throughout the dose interval in infants
with GA of 24 to 27 weeks [4].
Surgical Prophylaxis
Less than 1.2 kg: Single 7.5 mg/kg IV dose 60 minutes before surgical incision. Re-dose if
the procedure exceeds 2 half-lives of metroNIDAZOLE or there is excessive blood loss during
the procedure. If continued postoperatively, the duration should be less than 24 hours,
regardless of the presence of intravascular catheters or indwelling drains [5].
1.2 kg or more: Single 15 mg/kg IV dose 60 minutes before surgical incision. Re-dose if the
procedure exceeds 2 half-lives of metroNIDAZOLE or there is excessive blood loss during the
procedure. If continued postoperatively, the duration should be less than 24 hours,
regardless of the presence of intravascular catheters or indwelling drains [5].
Dosage Adjustment
Severe Hepatic Impairment (Child-Pugh C): Reduce dose by 50% [6][7].
Uses
Anaerobic Infections: Metronidazole is effective for anaerobic infections and protozoal

parasites but it is not approved in infants [6][7]. Common uses in premature infants are for
the treatment of anaerobic bacteremia and central nervous system infections [9].
Clostridium difficileinfection: Young children and infants may be asymptomatically

https://www.micromedexsolutions.com/micromedex2/librarian/CS/A74A5C/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/6
503
colonized, but are unlikely to be infected with C difficile
. Routine testing for in C difficile
neonates or infants 12 months or younger with diarrhea is not recommended [10] .
Clinical Definition Recommendation

Initial episode, non-severe MetroNIDAZOLE or Vancomycin
Vancomycin +/- IV metroNIDAZOLE (when critical illness is
Initial episode, severe/fulminant
present)
First recurrence, non-severe MetroNIDAZOLE or Vancomycin
Vancomycin
•For 10 days followed by rifAXIMin* for 20 days OR
Second or subsequent
•As a tapered and pulsed regimen
recurrence
OR
Fecal microbiota transplantation (after multiple recurrences)
McDonald, 2017
* Pediatric dosing not available for rifAXIMin; no FDA approved uses for patients younger than 12
years.
Necrotizing enterocolitis: The recommended IV broad-spectrum antibiotics are a

combination of ampicillin, gentamicin, and metroNIDAZOLE; ampicillin, cefotaxime, and
metroNIDAZOLE; or meropenem. Vancomycin is an alternative to ampicillin when MRSA or
ampicillin-resistant enterococcal infection is suspected [11].
Administration
Intravenous:
•Infuse over 30 to 60 minutes at a final concentration not to exceed 8 mg/mL (administer by
slow IV drip infusion only, either as a continuous or intermittent infusion) [8].
•Do NOT use equipment containing aluminum (eg, needles, cannulae) that would come in
contact with the drug solution [8].
•Do not introduce additives into injection; if used with a primary IV fluid system, discontinue
the primary solution during infusion [8].
MEDICATION SAFETY
Contraindications[6][7][18]
Alcohol (or products containing propylene glycol) use during and for at least 3 days
after metroNIDAZOLE use (oral, Flagyl(R) IV)
Concomitant use with or within the last 2 weeks of disulfiram (oral, Flagyl(R) IV)
Hypersensitivity to metroNIDAZOLE or any other component of the product or to other
nitroimidazole agents
Precautions
Cardiovascular: Sodium retention may occur in patients who are predisposed to edema
504
(IV) [6][7][18]
Hematological: Mild leukopenia has been observed during drug administration; use
cautiously in patients with evidence or history of blood dyscrasia and monitoring
recommended (IV, oral) [6][7][18]
Hepatic: Accumulation of metroNIDAZOLE in patients with hepatic impairment may occur;
dose adjustment recommended for severe impairment, monitoring for mild or moderate
impairment (IV, oral) [6][7][18]
Immunological: Use in absence of bacterial or parasitic infection, active or suspected, or
prophylactic indication may result in increased risk of drug-resistant bacteria or parasites (IV,
oral) [6][7][18]
Immunological: Candidiasis, known or previously unrecognized, including vaginal
candidiasis, may present with more prominent symptoms during treatment (IV, oral) [6][7]
[18]
Laboratory test interference: May occur with some serum chemistry values (eg, AST,
ALT, lactate dehydrogenase, triglycerides, glucose hexokinase); values of zero may be
observed (IV, oral) [6][7][18]
Neurological: Encephalopathy, associated with cerebellar toxicity characterized by ataxia,
dizziness, and dysarthria, has been reported (IV, oral); if abnormal neurologic signs occur,
evaluate benefit to risk ratio for continued therapy; prompt discontinuation may be required
[6][7][18]
Neurological: Peripheral neuropathy, including optic neuropathy, has been reported (IV,
oral); if abnormal neurologic signs occur, evaluate benefit to risk ratio for continued therapy;
prompt discontinuation may be required [6][7][18]
Neurological: Convulsive seizures have been reported (IV, oral); if abnormal neurologic
signs occur, evaluate benefit to risk ratio for continued therapy; prompt discontinuation may
be required [6][7][18]
Neurological: Aseptic meningitis has been reported (IV, oral); if abnormal neurologic signs
occur, evaluate benefit to risk ratio for continued therapy; prompt discontinuation may be
required [6][7][18]
Renal: Drug or metabolites may accumulate in patients with renal disease or ESRD;
monitoring recommended (IV, oral) [6][7][18]
Special populations: Increased risk of hepatotoxicity, including fatal cases, after initiation
of treatment in patients with Cockayne syndrome. Use in these patients only after careful
risk/benefit assessment and discontinue use if liver function tests are elevated [15][16][17].
Adverse Effects
The most common adverse reactions are related to the gastrointestinal tract, particularly
nausea, sometimes accompanied by headache, anorexia, and occasionally vomiting, diarrhea,
epigastric distress, abdominal cramping, and constipation [8]
Black Box Warning
MetroNIDAZOLE has been shown to be carcinogenic in mice and rats. Unnecessary use of the
drug should be avoided. Its use should be reserved for the conditions described in the
Indications and Usage section of the package insert [6].
505
D5W, and NS.
Manufacturer recommends that if metroNIDAZOLE is used with a primary IV fluid system, the
primary solution should be discontinued during metroNIDAZOLE infusion.
Acyclovir, amikacin, amiodarone, ampicillin, caspofungin, cefazolin, cefepime, cefotaxime,

cefoxitin, ceftazidime, ceftriaxone, chloramphenicol, clindamycin, dopamine, enalaprilat,
esmolol, fluconazole, gentamicin, heparin, hydrocortisone succinate, linezolid, lorazepam,
magnesium sulfate, midazolam, milrinone, morphine, netilmicin, nicardipine, penicillin G,
piperacillin-tazobactam, prostaglandin E1, remifentanil, and tobramycin.
Aztreonam and meropenem.
Monitoring
•Consider culture and susceptibility information before treatment initiation and with therapy
modifications whenever possible [8][12][13][14].
•Confirm trichomonad infection with wet smears, cultures, or both before treatment
initiation. Repeat cultures or smears after treatment cessation to confirm eradication and
before repeated treatment [12][14].
•Perform total and differential leukocyte counts both before and after therapy [12][14][13]
and in patients who require prolonged or repeated treatment [8].
•Monitor patients with ESRD or hepatic impairment for drug-associated adverse events [12]
[14].
Monitor geriatric patients for drug-associated adverse events [12][14].
•In patients with Cockayne syndrome, obtain a liver function test prior to therapy initiation,
within the first 2 to 3 days after initiation, frequently during therapy, and after discontinuing
therapy [15][16][17].
•Observe patients with Cockayne syndrome for signs and symptoms for potential liver injury
(eg, abdominal pain, nausea, change in stool color, or jaundice) [16][15][17].
506
Pharmacology
Mechanism of action
MetroNIDAZOLE is bactericidal for many anaerobic organisms. The drug exhibits
concentration-dependent bactericidal activity with a post-antibiotic effect of greater than 3
hours [19].
Pharmacokinetics
Absorption: Oral metroNIDAZOLE is well absorbed [6].
Distribution
Volume of distribution: Median Vd was 0.71 L/kg for 32 infants with a median gestational
age of 27 weeks (median postnatal age of 41 (0 to 97) days; postmenstrual age 32 (24 to
43) weeks; and weight 1,4954 (678 to 3,850) g). [3].
Concentration is CSF is similar to concentration in plasma [6].
Protein-binding: less than 20% protein bound [6].
Metabolism: Newborns have diminished capacity to eliminate metroNIDAZOLE [6]
Clearance: Median clearance parameters for 32 infants were: [3].
0.024 L/hrs/kg; gestational age of less than 26 (median postnatal age, 53 days (7 to 97
days))
0.026 L/hrs/kg; gestational age 26 to 29 weeks (median postnatal age, 32 days (0 to 97
days))
0.029 L/hrs/kg; gestational age 30 to 32 weeks (median postnatal age, 33 days (8 to 71
days))
Half-life: Median half-lives for 32 infants were: [3].
20.5 hours; gestational age of less than 26 (median postnatal age, 53 days (7 to 97
days))
18.6 hours; gestational age 26 to 29 weeks (median postnatal age, 32 days (0 to 97
days))
16.7 hours; gestational age 30 to 32 weeks (median postnatal age, 33 days (8 to 71
days))
ABOUT
Injection
Availability: 5 mg/mL in 100 mL single-dose plastic ready-to-use solution containers and
500-mg vials.
Storage: For the ready-to-use solution, protect from light until use and store at
controlled room temperature. Do not refrigerate (crystals form, but redissolve on
warming to room temperature). For the vial store below 77 degrees F and protect
from light.
Reconstitution of Vial: Add 4.4 mL of bacteriostatic water for injection, 0.9%
sodium chloride, or bacteriostatic 0.9% sodium chloride for a final concentration
of approximately 100 mg/mL. The pH is 0.5 to 2. Solution must be further diluted
and neutralized. Reconstituted vials are stable for 96 hours when stored below 86
degrees F in room light [8].
507
Dilution and Neutralization (vial product)
Dilution: Add to glass or plastic IV container not to exceed 8 mg/mL. May use
0.9%, D5W, or lactated ringer's injection [8].
Neutralization: Neutralize the solution with 5 mEq of sodium bicarbonate
injection for each 500 mg of metroNIDAZOLE used. Mix thoroughly. The resultant
pH should be 6 to 7. Relieve any gas pressure due to the generation of carbon
dioxide accumulation from the neutralization pressure. Do not refrigerate
neutralized solution; precipitation may occur . Use within 24 hours of mixing [8].
Oral
Availability: 250-mg and 500-mg tablets for oral administration.
Extemporaneous Oral Suspension

Oral suspension 15 mg/mL may be prepared by crushing thirty (30)
metroNIDAZOLE 250-mg tablets (7500 mg), dissolving powder in 10 mL Water for
Irrigation, then adding chocolate-cherry syrup* to make a total volume of 500
mL. Shake well. Suspension is stable for 60 days refrigerated.
*Chocolate-cherry syrup: Add 0.6 mL artificial wild cherry flavor to 300 mL simple
syrup BP, mix well. Then add chocolate syrup (Nestle Quik®) to cherry syrup to a
total volume of 500 mL, mix well. This suspension was judged most palatable
versus a chocolate, wild cherry, or plain suspension [20].
Oral suspension 50 mg/mL may be prepared by adding 12 mL of the vehicle* to 6

grams metroNIDAZOLE powder (equivalent to twenty-four (24) 250-mg tablets)
in a mortar and mix to a uniform paste. Add the vehicle in geometric portions and
mix thoroughly after each addition. Transfer the contents of the mortar to the
calibrated bottle. Add vehicle to the total volume of 120 mL. Protect from light.
Shake well. Suspension is stable for 60 days refrigerated or at room temperature
(5 and 25 degrees C).
*Vehicles: 1:1 mixture of Ora-Sweet® and Oral-Plus®; 1:1 mixture of Ora-Sweet®

SF and Oral-Plus®; or cherry syrup (cherry syrup concentrate diluted 1:4 with
simple syrup) [21].
508
Micafungin
Dose
Acute Disseminated Candidiasis

Without meningoencephalitis and/or ocular dissemination: 4 mg/kg IV once daily
[1].
Candida Peritonitis and Abscess

[1].
Candidemia
[1].
Duration of therapy for candidemia, without metastatic complications, is 2 weeks after
documented clearance of Candida
from the bloodstream and resolution of symptoms [2].
Uses
Neonatal Candidiasis, Including CNS Infection[2]

Invasive candidiasis and candidemia, or very low-birth weight infants with asymptomatic
candiduria .
Amphotericin B deoxycholate is recommended.
Fluconazole IV or oral is an alternative for those who have not been receiving
prophylaxis with fluconazole.
Lipid formulation amphotericin B agent is an alternative; however, use with caution,
especially in the presence of urinary tract involvement.
Echinocandins (caspofungin, anidulafungin, or micafungin) should be limited to salvage
therapy or scenarios of resistance or toxicity to amphotericin B deoxycholate or
fluconazole
Central nervous system infections

Liposomal amphotericin B agent is an alternative.
Salvage therapy with flucytosine may be added in those patients who have not
responded to initial therapy.
Fluconazole may be used as step-down therapy for fluconazole-susceptible isolates in
those patients who respond to initial therapy
Neonatal intensive care unit (with greater than 10% rate of invasive candidiasis)
Prophylaxis with IV or oral fluconazole for 6 weeks is recommended for neonates with
birth weights of less than 1000 g
509
Prophylaxis with oral nystatin is an alternative in neonates with birth weights of less
than 1500 g when fluconazole is unavailable or fluconazole resistance is present
Comparison to Amphotericin B: There was no difference in clinical response between

echinocandins and amphotericin B (OR 1.38; 95% CI, 0.68 to 2.8) for the treatment of
suspected or confirmed invasive candidiasis in a meta-analysis (n=5; 354 neonates and
children). Antifungals included were micafungin, caspofungin, amphotericin B deoxycholate,
and liposomal amphotericin B. Subanalysis demonstrated no difference in other comparisons
including mycological response, mortality, recurrence of candida infection, type of
echinocandin, different risk groups (high-risk, low-risk, or neutropenic groups), and type of
use (targeted or empirical). Discontinuation due to adverse effects were higher with
amphotericin B than the echinocandins (OR 0.3; 95% CI, 0.12 to 0.76) [5].

Micafungin is indicted for: [1]
Acute disseminated candidiasis without meningoencephalitis and/or ocular
dissemination in pediatric patients younger than 4 months
Candida peritonitis or abscesses without meningoencephalitis and/or ocular
dissemination in pediatric patients younger than 4 months
Candidemia in pediatric patients younger than 4 months without meningoencephalitis
and/or ocular dissemination
•The safety and effectiveness of micafungin for the treatment of candidiasis (acute
disseminated and candidemia) without meningoencephalitis and/or ocular dissemination in
patients younger than 4 months is based on evidence from studies in adult and pediatric
patients 4 months or older with additional pharmacokinetic and safety data in pediatric
patients younger than 4 months
Limitations:[1]
Safety and effectiveness of micafungin have not been established for the treatment of
candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients
younger than 4 months of age as a higher dose may be needed
Micafungin has not been adequately studied in patients with endocarditis, osteomyelitis
and meningoencephalitis due to Candida
Efficacy of micafungin against infections caused by fungi other than Candida has not
been established
Administration
Administer by intermittent IV infusion over 1 hour at a concentration between 0.5 to 1.5

mg/mL [3]. The recommended concentration is 1 mg/mL [4]. Existing IV line should be
flushed with NS prior to administration. Concentrations higher than 1.5 mg/mL (up to 4
mg/mL) should be administered through a central line [3].
MEDICATION SAFETY
510
Hematologic: Acute intravascular hemolysis and hemolytic anemia have been reported [6].
Hepatic: Hepatic abnormalities (eg, liver function test (LFT) abnormalities, significant
hepatic impairment, hepatitis, hepatic failure) have occurred. Evaluate risk vs benefit of
continued treatment if abnormal liver function tests develop [6].
Immunologic: Hypersensitivity reactions (eg, anaphylaxis, shock) have been reported.
Discontinue use if hypersensitivity occurs and institute appropriate treatment [6]
Immunologic: Infusion reactions have been reported including rash, pruritus, facial
swelling, and vasodilatation; slow the infusion rate if reaction occurs [1]
Immunologic: Injection site reactions, including phlebitis and thrombophlebitis, have been
reported with doses of 50 to 150 mg/day; occurs more often in patients receiving micafungin
via a peripheral IV [1]
Renal: Hemoglobinuria and renal dysfunction (eg, BUN or creatinine elevations, significant
renal impairment, acute renal failure) have been reported [6].
Adverse Effects
Most common adverse events (2% to 3%) reported in pediatric clinical trials were
hypokalemia, increases in AST, ALT, bilirubin, or alkaline phosphatase levels, abnormal liver
function tests, and hypertension. More severe hepatic dysfunction, hepatitis, and hepatic
failure have also been reported. Pediatric patients (especially less than 1 year of age) appear
to be at higher risk than adults for developing liver injury. Neutropenia, thrombocytopenia,
and hypomagnesemia also occurred in less than 2% of patients. Other common adverse
events include nausea, vomiting, diarrhea, and rash [7][8][9].
D5 W, D5 1/4 NS, LR, and NS.
Micafungin diluted to 1.5 mg/mL

Aminophylline (2.5 mg/mL), bumetanide (40 mcg/mL), calcium chloride (40 mg/mL), calcium
gluconate (40 mg/mL), cyclosporine (5 mg/mL), dopamine (3.2 mg/mL), esmolol 10 mg/mL),
furosemide (3 mg/mL), heparin (100 units/mL), hydromorphone (0.5 mg/mL), lidocaine (10
mg/mL), lorazepam (0.5 mg/mL), magnesium sulfate (100 mg/mL), milrinone (0.2 mg/mL),
nitroglycerin (0.4 mg/mL), potassium chloride (0.1 mEq/mL), sodium nitroprusside (2
mg/mL), tacrolimus 20 mcg/mL), theophylline (4 mg/mL), vasopressin (1 unit/mL).
Albumin, amiodarone, diltiazem, dobutamine, epinephrine, insulin, labetalol, levofloxacin,

midazolam, morphine, mycophenolate mofetil, nicardipine, octreotide, ondansetron,
511
phenytoin, rocuronium, and vecuronium.
Monitoring
Assess IV site for signs of irritation. Periodic measurement of serum potassium, calcium,
BUN, hepatic transaminases, and creatinine (isolated renal dysfunction reported in adults).
For candidemia, monitor blood cultures daily or every other day until Candida
is cleared [2].
Pharmacology
Mechanism of Action: Micafungin is a semisynthetic lipopeptide echinocandin antifungal

agent with broad-spectrum fungicidal activity against many Candida
species. It inhibits the
synthesis of 1, 3-beta-D-glucan, an integral component of the fungal cell wall [10].
Pharmacokinetics
The volume of distribution is relatively high in extremely premature infants, necessitating
higher doses. Plasma protein binding is high, primarily to albumin, but it does not displace
bilirubin. Pharmacokinetics are linear. Metabolism occurs primarily in the liver through both
noncytochrome and cytochrome P450 pathways to 2 biologically inactive metabolites that are
eliminated in the feces. A population pharmacokinetic analysis of pooled data from 47
neonates and young infants (weight range 0.54 to 4.5 kg) revealed a weight-adjusted
clearance that was higher than that reported for older infants and adults (0.043 L/hr/kg vs
0.017 L/hr/kg), which would necessitate use of a higher mg/kg/day dosage to achieve
comparable systemic AUCs [11]. Serum half-life ranges from 7 to 16 hours in neonates
(mean 11 hours). Mutant strains of Candida
with reduced susceptibility have been identified
in some adult patients during treatment suggesting the potential development of drug
resistance. Animal studies suggest tissue penetration to common sites of invasive fungal
infections: liver, spleen, kidney, and lungs. No cerebrospinal fluid levels were detected but
brain tissue levels were measurable.
The predicted AUC0 to 24 hours was 336 mg x hr/L with a 10-mg/kg/day IV dose in 18
neonates (ranges: gestational age 26.9 to 39 weeks, postnatal age 0.107 to 6.07 months)
[12].
In 12 neonates (median birth weight 775 g, gestational age 27 weeks, and 4 days postnatal),
15 mg/kg/day IV for 5 days resulted in a mean AUC0 to 24 hours of 437.5 mcg x hr/mL, CL of
0.0365 L/hr, and VSS of 1.6 L. A 15-mg/kg/day IV dose in this population was suggested to
correlate with 5 mg/kg/day IV in adults [13].
A population pharmacokinetic analysis of serum level data from 47 neonates who received
micafungin in 3 clinical trials determined that a dose of 10 mg/kg was required to achieve a
targeted MIC/AUC ratio in simulated patients for most strains of Candida albicans
. For more
resistant strains having a higher MIC of 0.125 mg/L, a dose of 12 mg/kg produced the
targeted AUC/MIC ratio in approximately 90% of simulated patients [11].
Extracorporeal Membrane Oxygenation (ECMO):The pharmacokinetic parameters were

512
clearance 0.041 L/kg/hr, Vd 0.64 L/kg, and half-life 11 hours for micafungin in infants
(median 59 days (0 to 574 days); gestational age 39 weeks (27 to 39 weeks)) supported by
ECMO (n=12). The AUC (0 to 24 hours) was 74 mgXhr/L for the 11 infants on 4 mg/kg/day of
IV micafungin. The ECMO circuits used were S3 and CardioHelp. Dose simulations predicted
AUC(0 to 24 hours) of 37.5 to 69.5 mgXhr/L within 24 hours with 2.5 mg/kg/day infused over 1
hour and 75 to 139 mgXhr/L with 5 mg/kg/day [14].
ABOUT
Available: Single-use lyophilized powder for injection in vials containing 50 and 100 mg.
Preservative free.
Reconstitution: Add 5 mL of 0.9% sodium chloride injection (without bacteriostatic agent)
or D5W to each 50 mg or 100 mg vial yielding approximately 10 mg or 20 mg per mL,
respectively. Inspect reconstituted vials for particulate matter and discoloration prior to
administration. Gently dissolve lyophilized powder by swirling the vial to avoid excessive
foaming. Do not shake [3].
Storage: Reconstituted vials may be stored at room temperature for up to 24 hours before
use. Protect from light. Discard partially used vials [3].
Dilution: Reconstituted drug should be further diluted in NS or D5 W to a final concentration

between 0.5 to 1.5 mg/mL prior to administration. Diluted infusion should be protected from
light and may be stored at room temperature for up to 24 hours before use. An existing IV
line should be flushed with NS prior to administration.
513
Microlipid®
Dose
Microlipid is a 50% safflower oil fat emulsion with 4.5 calories/mL. Used to supplement
orally, or added to tube feeding formulas. Mixes easily with enteral formulas.
Pharmacology
Osmolality (mOsm/kg water): Not available
Supplied: 48 three ounce bottles per case.
Ingredients: Safflower oil, water, polyglycerol esters of fatty acids, soy lecithin, xanthan
gum, ascorbic acid.
Microlipid
per 15 mL per 89 mL
Nutrient per mL
(1 tbsp) (3 fl oz)
Calories 4.5 67.5 400
Protein, g 0 0 0
Fat, g 0.5 7.5 44
Carbohydrate, g 0 0.04 0
Water, g 0.45 6.7 40
Linoleic Acid, g 0.4 5.9 35
Fatty Acid Distribution

Polyunsaturated 78%
Monounsaturated 12%
Saturated 10%
PUFA:SFA 8:1
ABOUT
For oral use only. Do not give parenterally (IV). Shake well before opening. Opened
product should be recapped, refrigerated, and discarded after 5 days. Store unopened bottles
514
at room temperature. Protect from freezing.
515
Midazolam
Dose
Sedation:
IV: 0.05 to 0.15 mg/kg. Repeat as required, usually every 2 to 4 hours. May also be given
IM. Dosage requirements are decreased by concurrent use of narcotics.
Continuous IV infusion: 0.01 to 0.06 mg/kg per hour (10 to 60 mcg/kg/hour). Dosage
may need to be increased after several days of therapy because of development of tolerance
and/or increased clearance.
Intranasal: 0.2 to 0.3 mg/kg per dose using 5-mg/mL injectable form.
Sublingual: 0.2 mg/kg per dose using 5-mg/mL injectable form mixed with a small amount
of flavored syrup.
Oral: 0.25 mg/kg per dose using Versed® oral syrup.
Anticonvulsant:
Loading dose: 0.15 mg/kg (150 mcg/kg) IV, followed by maintenance dose.
Maintenance infusion: 0.06 to 0.4 mg/kg per hour (1 to 7 mcg/kg per minute).
Uses
Anesthesia induction
Sedative/hypnotic: Efficacy could not be validated and safety concerns were raised in a
review of 3 studies (n=146 preterm neonates) of continuous infusion midazolam (30 to 60
mcg/kg/hr) for procedural sedation in the neonatal intensive care unit [4].
Refractory seizures
Administration
Intravenous: Administer slow IV push over 10 minutes at a concentration of 1 to 5 mg/mL

[1][2]. The recommended standard neonatal concentration is 1 mg/mL [3]. For continuous
IV infusion, may dilute in NS or D5W to a concentration of 0.5 mg/mL. Caution should be
taken to avoid intra-arterial injection or extravasation [3][1][2].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/D75755/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/5
516
MEDICATION SAFETY
Contraindications
•Allergy to cherries (Oral syrup) [7]
•Acute narrow-angle glaucoma [8][9][1][10]
•Open-angle glaucoma, untreated [8]
Precautions
Cardiovascular: Hypotension is common when used in conjunction with narcotics, or
following rapid bolus administration [9][1][10]
Cardiovascular: Serious cardiorespiratory events, including cardiac arrest resulting in death
or permanent injury have been reported with use of midazolam [8]
Cardiovascular: Rarely hypotensive episodes requiring treatment during or after diagnostic
or surgical manipulations have been reported; increased risk in patients with hemodynamic
instability or in those premedicated with a narcotic [8].
Endocrine or metabolic: Use particular caution in uncompensated acute illness (eg, severe
fluid or electrolyte disturbances) [5]
Respiratory: Serious respiratory events including respiratory depression, airway obstruction,
oxygen desaturation, apnea, respiratory arrest, sometimes resulting in death or permanent
injury have been reported with use of midazolam; the risk is greatest in those with chronic
obstructive pulmonary disease, chronic disease states, or decreased pulmonary reserve, and
concomitant use of barbiturates, alcohol, or other CNS depressants [8].
Neurologic: CNS depression may occur; increased risk with concomitant use of alcohol,
other CNS depressants (eg, opioids), barbiturates, and moderate or strong CYP3A4 inhibitors
[8].
Neurologic: Partial or complete impairment of recall may exist for several hours following
an administered dose [8].
Neurologic: Brain development in children may be affected by repeated or lengthy use of
general anesthetic and sedation drugs during surgeries or procedures, especially in children
younger than 3 years or in fetuses of pregnant women during the third trimester; balance
appropriate anesthesia use and timing of elective procedures that can be delayed against
potential risks in children younger than 3 years and pregnant women, particularly with
procedures that are longer than 3 hours or multiple procedures [11].
Ophthalmic: May increase intraocular pressure in patients with glaucoma; may be used in
patients with open-angle glaucoma only if they are receiving appropriate therapy; monitoring
is recommended [8].
Psychiatric: Antiepileptic drugs, including midazolam, may increase the risk of suicidal
thoughts or behavior; monitoring is recommended [8].
Psychiatric: Agitation, involuntary movements (including tonic/clonic movements and
muscle tremor), hyperactivity, and combativeness have been reported with midazolam when
used for sedation; consider the possibility of cerebral hypoxia or true paradoxical reactions
[8].
Respiratory: Serious respiratory events including respiratory depression, airway obstruction,
oxygen desaturation, apnea, respiratory arrest, sometimes resulting in death or permanent
injury have been reported with use of midazolam; the risk is greatest in those with chronic
obstructive pulmonary disease, chronic disease states, or decreased pulmonary reserve, and
concomitant use of barbiturates, alcohol, or other CNS depressants [8].
Special populations: Gasping syndrome or other severe or fatal adverse effects can occur
in neonates and low birth weight infants, as formulation contains benzyl alcohol [6]
Surgery: Risk of desaturation and hypoventilation from partial airway obstruction increased in
517
pediatric patients undergoing procedures involving upper airway (eg, upper endoscopy,
dental care); those with cardiac or respiratory compromise may be unusually sensitive.
Dosage adjustment may be required in higher-risk patients [5][12]
Withdrawal: Symptoms of withdrawal have occurred following discontinuation [5][12]
Adverse Effects
Respiratory depression and hypotension are common when used in conjunction with
narcotics, or following rapid bolus administration. Seizure-like myoclonus has been reported
in 8% of premature infants receiving continuous infusions - this also may occur following
rapid bolus administration and in patients with underlying CNS disorders. Nasal
administration may be uncomfortable because of a burning sensation.
Black Box Warning
Midazolam has been associated with respiratory depression and respiratory arrest, especially
when used for sedation in noncritical care settings. Use only in settings that can provide for
continuous monitoring of respiratory and cardiac function. The initial dose and all subsequent
doses should always be titrated slowly [5]. Concomitant use of benzodiazepines and opioids
may result in profound sedation, respiratory depression, coma, and death. Monitor patients
for respiratory depression and sedation [6].
Midazolam hydrochloride should not be administered by rapid injection in the neonatal

population. Severe hypotension and seizures have been reported following rapid IV
administration, particularly with concomitant use of fentanyl [5].
D5W, NS, and sterile water for injection.
Amikacin, aminophylline, amiodarone, atropine, calcium gluconate, cefazolin, cefotaxime,

cimetidine, clindamycin, digoxin, dobutamine, dopamine, epinephrine, erythromycin
lactobionate, esmolol, famotidine, fentanyl, fluconazole, gentamicin, glycopyrrolate, heparin,
imipenem/cilastatin, insulin, linezolid, lorazepam, methadone, metoclopramide,
metronidazole, milrinone, morphine, nicardipine, nitroglycerin, nitroprusside, pancuronium
bromide, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, theophylline,
tobramycin, vancomycin, and vecuronium.
518
Fat emulsion. Albumin, ampicillin, bumetanide, cefepime, ceftazidime, dexamethasone,
fosphenytoin, furosemide, hydrocortisone succinate, micafungin, nafcillin, and sodium
bicarbonate.
Monitoring
Follow respiratory status and blood pressure closely, especially when used concurrently with
narcotics. Assess hepatic function. Observe for signs of withdrawal after discontinuation of
prolonged therapy.
Pharmacology
Mechanism of action: Relatively short-acting benzodiazepine with rapid onset of action.

Sedative and anticonvulsant properties related to GABA accumulation and occupation of
benzodiazepine receptor. Antianxiety properties related to increasing the glycine inhibitory
neurotransmitter [9][1].
Metabolized by hepatic CYP 3A4 to a less active hydroxylated metabolite, then

glucuronidated before excretion in urine. Drug accumulation may occur with repeated doses,
prolonged infusion therapy, or concurrent administration of cimetidine, erythromycin or
fluconazole. Highly protein bound. Duration of action is 2 to 6 hours.
Elimination half-life is approximately 4 to 6 hours in term neonates, and quite variable, up
to 22 hours, in premature babies and those with impaired hepatic function.
Bioavailability is approximately 36% with oral administration and 50% with sublingual and
intranasal administration.
Midazolam is water soluble in acidic solutions and becomes lipid soluble at physiologic pH [9]
[1][13][14][15].
ABOUT
Injectable
Available: preservative-free 1- and 5-mg/mL concentrations in 1-, 2-, and 5-mL vials. Also
available in an injectable form as 1- and 5-mg/mL concentrations in 1-, 2-, 5-, and 10-mL
vials which contain 1% (10 mg/mL) benzyl alcohol as a preservative.
Stability:
Stable for 24 hours when diluted with NS or D5W to a concentration of 0.5 mg/mL; stable for
4 hours in LR [1].
At least 95% of the initial concentration of midazolam remained on day 100 when midazolam
5 mg/mL and midazolam 0.4 mg/mL in D5W were stored at room temperature in
519
polypropylene syringes [16].
Oral
Available: Oral syrup 2 mg/mL.
Storage:Store at room temperature [9].
Intranasal
Availability: Single-dose nasal spray unit delivers 5 mg of midazolam in 0.1 mL of solution.
Storage: Store at a controlled room temperature between 20 and 25 degrees C (68 to 77
degrees F), with excursions permitted between 15 and 30 degrees C (59 to 86 degrees F) [8]
Other Routes
Injectable formulation was used for intranasal, buccal, or rectal administration [17][18][15].
520
Milrinone
Dose
Low Cardiac Output; Post-Cardiac Surgery

Loading dose: 50 mcg/kg IV over 15 minutes [1] or 75 mcg/kg IV infused over 60 minutes,
immediately followed by a maintenance infusion [2] has been used. In premature infants less
than 30 weeks gestational age, infuse loading dose over 3 hours.
Maintenance infusion: 0.3 [3] to 0.75 mcg/kg/minute [2] for 35 hours [2].
Note: Above doses are from studies that included mostly older infants and children for the
treatment or prevention of low cardiac output post-cardiac surgery.
Adjust infusion rate based upon hemodynamic and clinical response.
Uses
Low Cardiac Output Post-Cardiac Surgery; Prophylaxis: In one double-blind, placebo-

controlled study (n=238) in children after cardiac surgery, the relative risk reduction for the
prevention of low cardiac output syndrome was 55% (p=0.023) with milrinone (75 mcg/kg
bolus, followed by 0.75 mcg/kg/minute infusion) compared with placebo. The age range was
2 days to 6.9 years (median, 3 months) [2]. A transient increase in heart rate (149+/-13 to
163+/-12 beats/min) was observed in 10 neonates administered 50 mcg/kg loading dose
over 15 minutes; no neonate experienced sustained supraventricular tachyarrhythmias or
ventricular ectopy [1].
Low Systemic Blood Flow, Prevention: A randomized, placebo-controlled clinical trial

demonstrated milrinone was no more effective than placebo in preventing low systemic blood
flow in preterm neonates less than 30 weeks GA. Neonates received milrinone (started
before 6 hours of age) 0.75 mcg/kg/minute for the first 3 hours followed by 0.20
mcg/kg/minute until 18 hours of age. There was no difference in superior vena cava flow
between the milrinone and placebo groups. A heart rate of 160 beats/min or more occurred
in 67% of the milrinone-treated group and 22% of the placebo-treated group (p=0.0001)
[7].
Persistent Pulmonary Hypertension of the Newborn (PPHN): Low level evidence

exists for the use of milrinone for PPHN. The use of IV milrinone for infants with PPHN and
signs of left ventricular dysfunction may be considered [8]. Typically, reserved for severe
PPHN refractory to inhaled nitric oxide complicated by poor cardiac function on
echocardiogram [9]. In 5 observational studies, term neonates (n=47) with oxygen index
(OI) greater than 20 despite inhaled nitric oxide received IV milrinone. Improvements
observed were OI reduction, inhaled nitric oxide dose reduction, and indicators of myocardial
performance increase [10][11][12][13][14]. Transient nonsignificant decreases in systolic
arterial pressure [11], as well as reductions in blood pressure requiring vasopressor inotropes
have been observed [10]. Dose ranges were 0.33 to 0.99 mcg/kg/min with or without a
bolus dose of 50 mcg/kg over 60 minutes [10][11][12][13][14].
521
Severe Sepsis and Septic Shock[15]
Hemodynamic Support - First 60 Minutes

Time Management- Proceed to next step if shock persists
0
Maintain airway and establish access
minutes
Push 10 mL/kg isotonic crystalloid or colloid boluses up to 40 mL/kg until improved
5
perfusion or unless hepatomegaly.
minutes
Begin prostaglandin infusion until rule out ductal-dependent lesion.
15 DOPamine less than 10 mcg/kg/min +/- DOBUTamine for fluid-refractory shock
minutes EPINEPHrine 0.05 to 0.3 mcg/kg/min for fluid-refractory DOPamine-resistant shock
Cold shock-Poor LV function Add nitrovasodilator milrinone or inamrinone
Normal blood pressure with volume loading
ScvO(2) less than 70%*/Hgb greater than
12 g/dL
SVC flow less than 40 mL/kg/min or CI less
than 3.3 L/min/m(2)
Cold shock- Poor RV function Inhaled nitric oxide
PPHN Inhaled iloprost or IV adenosine
ScvO(2) less than 70%* IV milrinone or inamrinone
60 min than 3.3 L/min/m(2)
Titrate volume
Warm shock- Low blood pressure Add norepinephrine
Vasopressin or terlipressin or angiotensin
Hydrocortisone if absolute adrenal
insufficiency.
Triiodothyronine if hypothyroid.
Refractory shock
Begin pentoxifylline if VLBW newborn.
Consider closing PDA if hemodynamically
significant.
ECMO
Goals
•First Hour: restore and maintain heart rate thresholds, capillary refill of 2 seconds or less, and
normal blood pressure.
• NICU: normal MAP-CVP, preductal and postductal oxygen saturation difference less than 5%,
*ScvO(2) greater than 70% (except congenital heart patients with mixing lesions), SVC flow greater
than 40 mL/kg/min, or cardiac index greater than 3.3 L/min/m(2)
KEY: CI = cardiac index, Hgb = hemoglobin, LV function = left ventricle function, MAP-CVP = mean
arterial pressure-central venous pressure, PDA = patent ductus arteriosus, PPHN = persistent
pulmonary hypertension of the newborn, ScvO(2) = continuous central venous oxygen saturation,
SVC = superior vena cava, VLBW = very low birth weight
Davis et al: Crit Care Med 2017;45(6)
Administration
Administer loading dose over 15 to 60 minutes. May give undiluted or further dilute in
compatible diluent. For maintenance infusion, dilute in compatible solution to a maximum
concentration of 200 mcg/mL, or use available premixed solution for injection (100-mL
and 200-mL bags) [4][5]. May also be given by IO route if IV access unavailable [6][4].
522
In premature infants less than 30 weeks gestational age, infuse loading dose over 3 hours.
MEDICATION SAFETY
Adverse Effects
Assure adequate vascular volume prior to initiating therapy. Blood pressure will likely fall 5%
to 9% after the loading dose, but should gradually return to baseline by 24 hours. Heart rate
increases of 5% to 10% are also common. Thrombocytopenia was reported frequently in
some studies and rarely in others. Arrhythmias occur occasionally.
D5W, NS, and LR.
Acyclovir, amikacin, aminophylline, amiodarone, ampicillin, atracurium, atropine, bumetanide,

calcium chloride, calcium gluconate, cefazolin, cefepime, cefotaxime, ceftazidime, cimetidine,
clindamycin, dexamethasone, digoxin, dobutamine, dopamine, epinephrine, fentanyl,
gentamicin, heparin, insulin, isoproterenol, lorazepam, meropenem, methylprednisolone,
metronidazole, micafungin, midazolam, morphine, nicardipine, nitroglycerin, norepinephrine,
oxacillin, pancuronium, piperacillin, piperacillin/tazobactam, potassium chloride, propofol,
propranolol, ranitidine, sodium bicarbonate, sodium nitroprusside, theophylline, ticarcillin,
ticarcillin/clavulanate, tobramycin, vancomycin, and vecuronium.
Furosemide, imipenem/cilastatin and procainamide.
Monitoring
Continuous monitoring of blood pressure, heart rate and rhythm. Assess signs of cardiac
output. Carefully monitor fluid and electrolyte changes and renal function during therapy.
Monitor platelet counts.
For a full-term newborn, the target heart rate and perfusion pressure (mean arterial pressure
minus central venous pressure) are 110 to 160 beats/min and 55 mm Hg, respectively [15].
523
Pharmacology
Mechanism of action: Milrinone improves cardiac output by enhancing myocardial

contractility, enhancing myocardial diastolic relaxation and decreasing vascular resistance. It
acts via selective phosphodiesterase III inhibition that leads to increased intracellular cyclic
AMP, increased myocardial intracellular calcium, and increased reuptake of calcium after
systole. Vasodilatation is related to increased levels of cyclic GMP in vascular smooth muscle.
Unlike catecholamines, myocardial oxygen consumption is not increased.
Distribution
Protein Binding: 70% bound to plasma protein [5].
Vd: 576 mL/kg in preterm (26 weeks gestational age (range, 23 to 28 weeks)) infants (first
day of life) [16] and 560 mL/kg (0.56 L/kg) in 11 infants (mean gestation age 39.2 weeks) at
14 hours of age [11].
Elimination
Excretion: Primarily renally eliminated [5]
Clearance: 0.64 mL/kg/min in preterm (26 weeks gestational age (range, 23 to 28 weeks))
infants (first day of life) [16], 1.8 mL/kg/min (0.108 L/kg/hr) in 11 infants (mean gestation
age 39.2 weeks) 14 hours of age with PPHN [11] and 3.05 mL/min/kg (7.65 mL/min/3.4 kg)
in 6 infants with a median age of 2 days (1 to 9 days) (median gestational age 39 weeks)
administered IV milrinione for persistent pulmonary hypertension of the newborn (PPHN)
[17].
Half-life: 10.3 hours in preterm (26 weeks gestational age (range, 23 to 28 weeks)) infants
(first day of life) [16] and 4.1 hours in 11 infants (mean gestation age 39.2 weeks) 14 hours
of age [11].
Target Concentration and Dosages: Milrinone concentration of 150 to 200 ng/mL would
be achieved 80% of the time with a bolus dose of 0.73 mcg/kg/min for 3 hours followed by
0.16 mcg/kg/min maintenance infusion in preterm neonates after surgical closure of patent
ductus arteriosus in a simulation study [18]. A milrinone concentration of 180 to 300 ng/mL
was achieved in 10 preterm infants who received 0.75 mcg/kg/min for 3 hours IV followed by
0.2 mcg/kg/min until 18 hours of age for the prevention of low systemic blood flow [16]. The
steady state concentration of milrinone was 291 ng/mL in 11 infants (mean gestation age
39.2 weeks) 14 hours of age administered milrinone 50 mcg/kg IV over 60 minutes followed
by a median dose of 0.33 mcg/kg/min for PPHN for 24 hours [11]
ABOUT
Available in 1-mg/mL solution for injection in 10-, 20-, and 50-mL single-dose vials. Dilute
with compatible diluent prior to administration. Maximum concentration for infusion is
200 mcg/mL. Also available as premixed solution for injection (100-mL and 200-mL bags)
in a concentration of 200 mcg/mL in 5% Dextrose (pH of 3.2 to 4) [19][5].
524
525
Morphine
Dose
0.05 to 0.2 mg/kg per dose IV, IM, or subQ.

Repeat as required (usually every 4 hours).
Opioid dependence: Begin at most recent IV morphine dose equivalent. Taper 10% to
20% per day as tolerated. Oral dose is approximately 3 to 5 times IV dose.
Pain
Continuous infusion: Loading dose 100 mcg/kg IV followed by 10 mcg/kg/hour [1][2][3]
[4]; postoperatively may be increased further to 20 mcg/kg/hr [1].
Neonatal Abstinence Syndrome

Initial dose: 0.03 to 0.1 mg/kg per dose orally every 3 to 4 hours. Maximum dose 0.2
mg/kg[5][6][7]. Wean dose by 10% to 20% every 2 to 3 days based on abstinence scoring
[8][9][7].
Dosage Adjustment
Hypothermia, Therapeutic: Dose reduction of morphine administered for comfort and
analgesia may be necessary in neonates with hypoxic ischemic encephalopathy receiving
hypothermia therapy [10]. Dose simulations predicted morphine concentrations of 10 to 40
nanograms/mL in full-term neonates [11][10] receiving a 50 mcg/kg IV loading dose
followed by [11] continuous morphine infusion of 5 mcg/kg/hr IV [11][10] or an intermittent
dose of 40 to 50 mcg/kg/dose IV every 6 hours and a concentration of 10 nanograms/mL
with 2.5 mcg/kg/hr continuous IV dosing [10]. Due to large inter-patient variability, doses
may need to be increased or decreased [11].
Uses
Analgesia: There is insufficient evidence to support the routine use of opioids in

mechanically ventilated neonates to reduce pain in a systematic review (n=13 studies; 1505
neonates) [15][16].
Neonatal abstinence syndrome (NAS)[17][5].

Compared with buprenorphine: Sublingual buprenorphine reduced the duration of
treatment for neonatal abstinence syndrome compared with oral morphine (15 days vs 28
days; p less than 0.001) in a double-blind, double-dummy, single-center study (n=63).
Preterm infants and infants exposed to benzodiazepines in utero were excluded. Median
https://www.micromedexsolutions.com/micromedex2/librarian/CS/8416F0/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/9
526
length of hospital stay was 21 vs 33 days (p less than 0.001) and use of supplemental
phenobarbital was 15% vs 23% (p=0.36) for buprenorphine and morphine, respectively.
Rates of adverse events were not different between the 2 groups [20]
Compared with methadone: Methadone outperformed morphine for the treatment of NAS
in a multicenter, randomized, double-blind study of 116 term infants (median length of
hospital stay (LOS) (16 vs 20 days, p=0.005), LOS attributable to NAS (16 vs 19 days,
p=0.005), and length of drug treatment (11.5 vs 15 days, p=0.009)). Initial oral doses were
0.3 mg/kg/day for Finnegan score (FS) of 8 to 10, 0.5 mg/kg/day for FS of 11 to 13, 0.7
mg/kg/day for FS 14 to 16, and 0.9 mg/kg/day for FS of 17 or more. The total daily doses
were divided every 4 hours for morphine and every 8 hours for methadone. A nonalcoholic
solution of methadone was compounded [17].
Neonatal abstinence syndrome was treated for a median of 14 days with methadone
compared with 21 days for morphine (p=0.008) in a double-blind, randomized trial (n=78).
All neonates were 35 weeks gestational or more and prenatal exposure was either
methadone or buprenorphine [21].
Compared with cloNIDine: Overall, cloNIDine monotherapy for NAS appeared to be as
effective as morphine in a randomized, double-blind, pilot study of 31 neonates younger than
7 days (gestational age, 35 weeks or more). Rescue drugs were not necessary in any
neonate. The initial cloNIDine dose was 0.625 mcg/kg/dose orally every 3 hours with dose
titrations up to a maximum of 12 mcg/kg/day [22].
Opioid dependence [5][9].
Procedural Pain: Morphine 100 mcg/kg orally administered 60 minutes prior to retinopathy
of prematurity screening in non-ventilated premature (less than 32 weeks' gestation or with a
birthweight of less than 1501 g) infants produced adverse cardiorespiratory effects for an
average of 6 to 8 hours in a randomized blinded placebo-controlled trial (n=31). The study
was underpowered (early termination due to safety findings) to detect differences in efficacy
between morphine and placebo. Oxygen desaturation at 6 and 24 hours after procedure and
bradycardia episodes at 24 hours after procedure occurred significantly more in the
morphine-group than placebo-group. Apneic episodes requiring resuscitation with non-
invasive positive pressure ventilation within the 24 hours after administration occurred in
20% of the morphine-group and 0% in the placebo-group [23].
Sedation.
Administration
IV: The recommended standard concentrations of morphine solutions are 0.1 mg/mL for
continuous infusion and 0.1 and 0.5 mg/mL for intermittent infusions. Typically, morphine
intermittent infusion is administered over 15 to 30 minutes [12]. Intermittent morphine was
infused over 1 hour in some studies [13][14].
MEDICATION SAFETY
Contraindications[27][31][30][32]
527
Significant respiratory depression
Acute or severe bronchial asthma in a unmonitored setting or in the absence of
resuscitative equipment
Concurrent use of monamine oxidase inhibitors (MAOIs) or within the last 14 days
Known or suspected gastrointestinal obstruction, including paralytic ileus
Neuraxial administration contraindications include: infection at injection microinfusion
site, concomitant anticoagulant therapy, uncontrolled bleeding diathesis, or the
presence of any other concomitant therapy or medical condition which would render
epidural or intrathecal administration of medication especially hazardous.
Precautions
Abuse: Abuse of controlled-release capsules or tablets by parenteral route may result in
local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and
valvular heart injury due to the presence of talc [33][34].
Cardiovascular: Preexisting circulatory shock may reduce cardiac output and blood
pressure [35][36][33][29][34][37][38]; avoid use [35][36][33][29][34].
Cardiovascular: Severe hypotension, including orthostatic hypotension and syncope, in
ambulatory patients may occur; especially in patients with compromised ability to maintain
blood pressure; monitoring recommended [35][39][36][33][29][34][37][38][40][41];
consider alternative non-opioid analgesic if possible [36][33][29][34][37][38][40][41].
Concomitant use: Avoid concomitant use with mixed agonist/antagonist (eg, pentazocine,
nalbuphine, butorphanol) [35][36][33][29][34][38] or partial agonists (eg, buprenorphine)
[35][39][36][33][29][34].
Endocrine and metabolic: Opioids may rarely lead to adrenal insufficiency due to
inadequate amounts of cortisol. If adrenal insufficiency is suspected, perform diagnostic
testing, treat with corticosteroids if confirmed, wean patient off of opioid if appropriate, and
continue to assess adrenal function [35][42].
Gastrointestinal: Difficulty with swallowing may occur due to tablet stickiness and swelling,
including choking, gagging, regurgitation, and having a tablet stuck in the throat. Do not
presoak, lick, or wet tablets prior to use. Take tablets singly and immediately after placing in
the mouth with enough water to ensure complete swallowing; alternative therapy may be
required [35].
Gastrointestinal: Intestinal obstruction or exacerbation of diverticulitis may occur due to
tablet stickiness and swelling, especially in patients with a small gastrointestinal lumen (eg
esophageal or colon cancer); alternative therapy may be required [35].
Hepatic: Spasm of the sphincter of Oddi and increased serum amylase levels may occur in
patients with biliary tract disease [35][36][33][29][34][37][38][40][43][44]; monitoring
recommended [35][39][36][33][29][34].
Hepatic: Use caution with epidural administration in patients with hepatic dysfunction [32]
[25].
Hepatic: Respiratory depression, sedation, and hypotension may occur in patients with
cirrhosis; monitoring recommended [27][45]s and titrate slowly in this population [46][27]
Immunologic: Anaphylaxis has been reported [37].
IM administration: Use caution when injecting intramuscularly into chilled areas or in
patients with hypotension or shock, since impaired perfusion may prevent complete
absorption. If repeated injections are administered, an excessive amount may be suddenly
absorbed if normal circulation is re-established [47].
IV administration: Rapid intravenous administration may result in chest wall rigidity [32].
Neurologic: Impaired consciousness or coma; avoid use [35][39][36][33][29][34]
Neurologic: Potentially life-threatening serotonin syndrome may occur, particularly with
concomitant use of serotonergic drugs [42].
Neurologic: Cordotomy or other interruption of pain transmission pathways; discontinue
528
use prior to procedure [37]
Neurologic: Use caution in patients susceptible to intracranial effects of carbon dioxide
retention (eg, those with brain tumors or increased intracranial pressure) as reduced
respiratory drive may occur, further increasing intracranial pressure; monitoring
recommended [27][45]
Neurologic: Opioids may obscure the clinical course in patients with head injury [27][45].
Neurologic: Myoclonic-like spasm of lower extremities has been reported with intrathecal
doses of more than 20 mg/day [40][44].
Neurologic: Inflammatory masses such as granulomas, some of which have resulted in
serious neurologic impairment including paralysis, have been reported in patients receiving
continuous infusion of opioids via indwelling intrathecal catheter; monitoring recommended
[25].
Neurologic: Seizure disorders may be induced [35][36][33][29][34][38][40][41] or
aggravated [35][36][33][29][34][37][38][40][41]; monitoring recommended [35][39][36]
[33][29][34].
Prolonged use: Long-term use of opioids may be associated with decreased sex hormone
levels and symptoms such as reduced interest in sex, impotence, or infertility. Laboratory
evaluation may be warranted [42].
Renal: Urinary retention, which may persist 10 to 20 hours following single epidural or
intrathecal administration, is a frequently associated with neuraxial opioid administration,
more frequently in male patients than female patients. Urinary retention may also occur
during the first several days of hospitalization for the initiation of continuous intrathecal or
epidural morphine therapy; monitoring recommended and prompt intervention required [32]
[25].
Renal: Respiratory depression, sedation, and hypotension may occur in patients with renal
failure; monitoring recommended [27][45]; use lower starting dosages and titrate slowly in
this population [27][45]
Renal: Use caution with epidural administration in patients with renal dysfunction [32][25].
Respiratory: Patients with significant chronic obstructive pulmonary disease or cor
pulmonale, and those with a substantially decreased respiratory reserve, hypoxia,
hypercapnia, or pre-existing respiratory depression are at increased risk of decreased
respiratory drive, especially during treatment initiation and titration; monitoring
recommended, particularly during treatment initiation and titration or when using
concomitant drugs that depress respiration; may consider non-opioid therapy [27][45]
Respiratory: Severe respiratory depression up to 24 hours following epidural or intrathecal
administration has been reported [32][25]; single-dose neuraxial administration may result in
acute or delayed respiratory depression for periods at least as long as 24 hours [32].
Respiratory: Sleep-related breathing disorders including central sleep apnea and sleep-
related hypoxemia may occur and risk increases in a dose-dependent fashion; dose reduction
may be necessary [27][32].
Special populations: Fatal respiratory depression may occur in opioid-intolerant patients
[36][37].
Special populations: Debilitated patients are at increased risk for respiratory depression
[35][36][33][29][34][37][38]; monitor closely, particularly during treatment initiation and
titration or when using concomitant CNS depressants [35][39][36][33][29][34] and reduce
dosage if necessary [35][37][38][41].
Withdrawal: Abrupt withdrawal may result in severe withdrawal symptoms and should be
avoided [35][39][36][33][29][34][37][38][40][41]. Serious withdrawal symptoms, including
uncontrolled pain, psychological distress, and suicide, may occur upon sudden dose decrease
or discontinuation in patients who are physically dependent on opioid medications; do not
discontinue abruptly and create a patient-specific plan to taper the opioid gradually [48].
529
Adverse Effects
Naloxone should be readily available to reverse adverse effects. Marked respiratory

depression (decreases the responsiveness of the respiratory center to CO2 tension).
Hypotension and bradycardia. Transient hypertonia. Ileus and delayed gastric emptying.
Urine retention. Tolerance may develop after prolonged use; wean slowly. Seizures reported
in two infants who received bolus plus infusion.
Black Box Warning
Injection route, solution

Risk of Medication Errors: Improper or erroneous substitution of Infumorph(R) 200 or 500
(10 or 25 mg/mL, respectively) for regular Duramorph(R) (0.5 or 1 mg/mL) is likely to result
in serious overdosage, leading to seizures, respiratory depression, and death [25].
•Risks with Neuroaxial Administration: Single-dose neuraxial administration may result in
acute or delayed respiratory depression up to 24 hours. Because of the risk of severe adverse
reactions when Duramorph is administered by the epidural or intrathecal route of
administration, patients must be observed in a fully equipped and staffed environment for at
least 24 hours after the initial dose [26]and, as appropriate, for the first several days after
catheter implantation [25].
•Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory
depression may occur with use of morphine sulfate. Monitor for respiratory depression,
especially during initiation of morphine sulfate or following a dose increase. Because of delay
in maximum CNS effect with intravenously administered drug (30 min.), rapid IV
administration may result in overdosing [26].
•Addiction, Abuse, and Misuse: Morphine sulfate exposes patients and other users to the
risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess
each patient’s risk prior to prescribing morphine sulfate, and monitor all patients regularly for
the development of these behaviors and conditions [26].
Neonatal Opioid Withdrawal Syndrome: Prolonged use of morphine sulfate during pregnancy
can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not
recognized and treated, and requires management according to protocols developed by
neonatology experts. If opioid use is required for a prolonged period in a pregnant woman,
advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that
appropriate treatment will be available [25][26].
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants: Concomitant
use of opioids with benzodiazepines or other central nervous system (CNS) depressants,
including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Limit dosages and durations to the minimum required. Follow patients for signs and
symptoms of respiratory depression and sedation [25][26].
Oral route
•Risk of Medication Errors: Ensure accuracy when prescribing, dispensing, and administering
morphine sulfate oral solution. Dosing errors due to confusion between mg and mL, and
other morphine solutions of different concentrations can result in accidental overdose and
death [27].
•Addiction, Abuse, and Misuse: Morphine sulfate exposes users to risks of opioid addiction,
abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before
prescribing, and monitor regularly for development of these behaviors or conditions [27][28]
[28][29].
530
•Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS): To ensure that the
benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food
and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy
(REMS) for these products.
•Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory
depression may occur. Monitor closely, especially upon initiation or following a dose increase.
Instruct patients to swallow morphine sulfate extended-release capsules whole to avoid
exposure to a potentially fatal dose of morphine sulfate [27][28][28][29].
•Accidental Ingestion: Accidental ingestion of morphine sulfate, especially in children, can
result in a fatal overdose [27][28][28][29].
•Neonatal Opioid Withdrawal Syndrome: Prolonged use of morphine sulfate during pregnancy
can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not
recognized and treated. If opioid use is required for a prolonged period in a pregnant
woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure
that appropriate treatment will be available [27][28][28][29].
•Interaction with Alcohol: Alcohol consumption should be avoided while taking morphine
sulfate extended-release capsules. Consumption of alcohol may lead potentially fatal
overdoses of morphine [28].
•Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants: Concomitant
use of opioids and benzodiazepines or other CNS depressants may result in profound
sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for
patients with inadequate alternative treatment options. Limit dosages and durations to the
minimum required and follow patients for signs and symptoms of respiratory depression and
sedation [27][28][28][29].
Rectal, suppositories[30]
Morphine sulfate suppositories expose users to risks of opioid addiction, abuse, and misuse,
which can lead to overdose and death. Assess patient’s risk before prescribing and monitor
regularly for these behaviors or conditions.
Serious, life-threatening , or fatal respiratory depression may occur. Monitor closely,
especially upon initiation or following a dose increase
Accidental exposure of morphine sulfate suppositories, especially by children, can result in a
fatal overdose of opium
Prolonged use of morphine sulfate suppositories during pregnancy can result in neonatal
opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If
prolonged opioid use is required in a pregnant woman, advise the patient of the risk of
neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS)
depressants, including alcohol, may result in profound sedation, respiratory depression,
coma, and death. Reserve concomitant prescribing for use in patients for whom alternative
treatment options are inadequate; limit dosages and durations to the minimum required; and
follow patients for signs and symptoms of respiratory depression and sedation.
D5W, D10W, and NS.

For continuous infusions of morphine containing heparin: Use only NS; maximum
morphine concentration 5 mg/mL.
531
Acyclovir, alteplase, amikacin, aminophylline, amiodarone, ampicillin, atropine, aztreonam,

bumetanide, caffeine citrate, calcium chloride, caspofungin, cefotaxime, cefoxitin,
ceftazidime, ceftriaxone, chloramphenicol, cefazolin, cimetidine, clindamycin,
dexamethasone, digoxin, dobutamine, dopamine, enalaprilat, epinephrine, erythromycin
lactobionate, esmolol, famotidine, fentanyl, fluconazole, furosemide, gentamicin,
glycopyrrolate, heparin, hydrocortisone succinate, ibuprofen lysine, insulin, lidocaine,
linezolid, lorazepam, meropenem, metoclopramide, metronidazole, mezlocillin, midazolam,
milrinone, nafcillin, nicardipine, nitroglycerin, oxacillin, pancuronium bromide, penicillin G,
phenobarbital, piperacillin, piperacillin/tazobactam, potassium chloride, propofol, propranolol,
ranitidine, remifentanil, sodium bicarbonate, sodium nitroprusside, ticarcillin/clavulanate,
tobramycin, trimethoprim/sulfamethoxazole, vancomycin, vecuronium, and zidovudine.
Azithromycin, cefepime, micafungin, pentobarbital, and phenytoin.
Monitoring
Monitor respiratory and cardiovascular status closely. Observe for abdominal distention and
loss of bowel sounds. Consider urine retention if output is decreased. For infants
experiencing neonatal abstinence syndrome, monitor and score signs of drug withdrawal
using a published abstinence assessment tool such as the modified Neonatal Abstinence
Scoring System (Finnegan) or the Lipsitz tool [5][9].
Monitor patients susceptible to the intracranial effects of carbon dioxide retention (eg,
evidence of intracranial pressure or brain tumors) for signs and symptoms of sedation and
respiratory depression, particularly during initiation of therapy [24].
Pharmacology
Mechanism of action: Morphine is a narcotic analgesic that stimulates brain opioid

receptors. Increases venous capacitance, caused by release of histamine and central
suppression of adrenergic tone. GI secretions and motility decreased. Increases smooth
muscle tone [49].
Pharmacokinetics are widely variable, including a more than 4-fold variation in morphine
exposure in neonates (gestational age 36 to 41.3 weeks; median 39 weeks) with hypoxic
ischemic encephalopathy receiving hypothermia therapy [10].
Bioavailability: Morphine is 20% to 40% bioavailable when administered orally.
Vd: In 20 neonates (gestational age 36 to 41.3 weeks) with hypoxic ischemic
encephalopathy (HIE) receiving hypothermia therapy, morphine Vd was 8.02 L (coefficient
532
of variation, 49%) [10]
Metabolism: Morphine is converted in the liver to two glucuronide metabolites (morphine-6-
glucuronide and morphine-3-glucuronide) that are renally excreted. Morphine-6-glucuronide
(M6G) is a potent respiratory-depressant and analgesic. Morphine-3-glucuronide (M3G) is an
antagonist to the effects of morphine and morphine-6-glucuronide.
Clearance: In 20 neonates (gestational age 36 to 41.3 weeks) with hypoxic ischemic
encephalopathy (HIE) receiving hypothermia therapy, morphine clearance was 0.765 L/hr
+/- 10.9%. This was considered markedly lower compared with full-term normothermic
neonates younger than 7 days without HIE in other studies [10]
Half-life: Approximately 9 hours for morphine and 18 hours for morphine-6-glucuronide.
Steady state concentrations of morphine are reached by 24 to 48 hours.
Hypothermia: In neonates with hypoxic ischemic encephalopathy receiving hypothermia

therapy, morphine 2.5 mcg/kg/hr was predicted to achieve a concentration of 10
nanograms/mL [10], in contrast to a dose of 5 mcg/kg/hr at birth (term neonates, 3.3 kg)
and 8.5 mcg/kg/hr at 1 month (4 kg) in infants who underwent noncardiac surgery [50].
Surgery: In a pharmacokinetic analysis of 184 pediatric patients 0 to 3 years of age who

underwent noncardiac surgery and received morphine IV postoperatively, the Vd (L per 70
kg) was 84 at birth, 92 at 7 days, 112 at 30 days, 131 at 90 days, and 136 for older than 90
days up to 3 years. The clearance (L/hr per 70 kg) for the parent drug was 14.5 at birth,
17.4 at 7 days, 26.3 at 30 days, 43.1 at 90 days, 57.3 at 180 days, 67.8 at 365 days, and
71.1 at 1000 days. A predicted mean steady serum concentration of 10 nanogram/mL for
morphine may be achieved with morphine hydrochloride infusion at rates of 5 mcg/kg/hr at
birth (term neonates, 3.3 kg), 8.5 mcg/kg/hr at 1 month (4 kg), 13.5 mcg/kg/hr at 3 months
(6 kg), 18 mcg/kg/hr at 1 year (10 kg), and 16 mcg/kg/hr for children 1 to 3 years of age
(12 to 18 kg) [50].
ABOUT
Available
Injection: Strengths ranging from 0.5 to 50 mg/mL.
Stability: At least 95% of the initial concentration of morphine remained on day 100 when
morphine 1 mg/mL in NS or D5W was stored at room temperature in polypropylene syringes
[51].
Oral
Available: 2, 4, and alcohol-free 20 mg/mL oral morphine sulfate solutions. The 20 mg/mL
(100 mg/5 mL) oral solution is for use only in opioid-tolerant patients [52][52]. Available in
immediate-release tablets (15 mg and 30 mg) and various extended-release tablet and
capsule formulations (10 to 200 mg).
Extemporaneous Oral Solution

A 0.2 mg/mL oral morphine solution prepared with morphine elixir 2 mg/mL diluted with
distilled water and stored in amber, plastic syringes at 25° C was stable for 60 days[53].
A 0.4 mg/mL oral morphine solution may be made by diluting 2 mL of alcohol-free oral
morphine sulfate solution (2 mg/mL) in 8 mL of sterile water for irrigation. The solution is
533
stable for 60 days under room temperature. Protect from light [54].
534
Moxifloxacin
Dose
Ophthalmic
Bacterial Conjunctivitis
Vigamox®
Instill 1 drop into the affected eye 3 times daily for 7 days [1].
Uses
Pediatric FDA-Approved Indications

Ophthalmic
Treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:
Corynebacterium species, Micrococcus luteus, Staphylococcus aureus, Staphylococcus
epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri,
Streptococcus pneumoniae, Streptococcus viridans group, Acinetobacter lwoffii, Haemophilus
influenzae, Haemophilus parainfluenzae, and Chlamydia trachomatis[1].
Administration
Ophthalmic
For topical ophthalmic use only. Do not inject subconjunctivally or introduce directly into the
anterior chamber of the eye [1].
MEDICATION SAFETY
Hypersensitivity reaction may occur. Discontinue at first sign [1].

Prolonged use may result in overgrowth of nonsusceptible organisms [1].
Adverse Effects
Ophthalmic: The most frequently reported adverse events were conjunctivitis, decreased
visual acuity, keratitis, dry eye, ocular discomfort, ocular hyperemia, ocular pain, ocular
pruritus, subconjunctival hemorrhage, and tearing. Nonocular-related adverse events
https://www.micromedexsolutions.com/micromedex2/librarian/CS/36C84C/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/2
535
included fever, increased cough, infection, otitis media, pharyngitis, rash, and rhinitis [1].
Pharmacology
Ophthalmic
Mechanism of action
Moxifloxacin, a fluoroquinolone, has a mechanism of action that is different from macrolides,
aminoglycosides, and tetracyclines and may be active against pathogens that are resistant to
these antibiotics. There is no cross-resistance between moxifloxacin and these classes of
antibiotics; however, cross-resistance has been seen between systemic moxifloxacin and
some other quinolones [1].
ABOUT
Ophthalmic:
Availability: Available as 0.5% strength, with 3 mL in a 4-mL bottle [1].
Storage: Store between 2 and 25 degrees C (36 and 77 degrees F) [1].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/36C84C/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 2/2
536
Mupirocin
Dose
Cutaneous infections: Apply small amounts topically to affected areas 3 times daily.
Decolonization: Apply small amounts to anterior nares twice daily for 5 to 7 days.
Uses
Decolonization: Along with other infection control processes in a neonatal intensive care
unit (NICU), mupirocin decolonization may be used during outbreaks of Staphylococcus
aureus and in the management of colonized neonates at high risk for S aureus
infection [1].
In a retrospective cohort study in a single-institution NICU (with low-level endemic MRSA),
22% (95% CI 4% to 37%) of MRSA acquisition could be attributed to MRSA carriers who
were untreated [2]. Decolonization, which included intranasal mupirocin, of MRSA-colonized
neonates (n=522) decreased the risk of gram-positive infections with no increased risk of
gram-negative infection in a multicenter, retrospective NICU study [3].
Topical use for skin infections caused by Staphylococcus aureus, S epidermidis, S

saprophyticus, and Streptococcus pyogenes.
MEDICATION SAFETY
Use of Bactroban(R) ointment is not recommended with conditions in which absorption of

large quantities of polyethylene glycol may occur, particularly in the presence of moderate or
severe renal impairment [4]. Bactroban(R) ointment and cream are not for use on mucosal
surfaces [4][5]. Discontinue use if sensitization or severe local irritation occur. Avoid contact
with eyes and rinse thoroughly if accidental contact occurs [4][6][5].
Systemic allergic reactions, which may be severe, have been reported, including anaphylaxis,
urticaria, angioedema, and rash [7].
Overgrowth of nonsusceptible organisms, including fungi, may occur with prolonged use.
Clostridium difficile-associated diarrhea has been reported; evaluate and institute appropriate
medical management if suspected or confirmed. Discontinuation may be warranted [4][6][5].
Avoid use of mupirocin nasal ointment with other intranasal products [6].
Adverse Effects
https://www.micromedexsolutions.com/micromedex2/librarian/CS/F74BA2/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/2
537
Use only on the skin. No adverse effects reported from topical administration. Routine use
may lead to selective bacterial resistance.
Monitoring
Assess affected area for continued infection.
Pharmacology
Topical antibacterial produced by fermentation of the organism Pseudomonas fluorescens.

Inhibits protein synthesis by bonding to bacterial isoleucyl-transfer-RNA synthetase. Highly
protein bound. Not absorbed into the systemic circulation after topical administration (older
infants and children). Metabolized in the skin to an inactive compound and excreted.
ABOUT
Available in unit-dose packets and 15 and 30-g tubes as a 2% ointment and cream (20
mg/g).
https://www.micromedexsolutions.com/micromedex2/librarian/CS/F74BA2/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 2/2
538
Nafcillin
Dose
Usual dosage: 25 mg/kg/dose IV.

Meningitis: 50 mg/kg/dose IV.
Antibiotic Dosing Chart:

Renal function and drug elimination are most strongly correlated with Postmenstrual Age
(PMA; equivalent to Gestational Age plus Postnatal Age). PMA is the primary determinant of
dosing interval, with Postnatal Age as the secondary qualifier.
Dosing Interval Chart

PMA PostNatal Interval
(weeks) (days) (hours)
0 to 28 12
≤29
>28 8
0 to 14 12
30 to 36
>14 8
0 to 7 12
37 to 44
>7 8
≥45 ALL 6
Uses
Penicillinase-producing staphylococci infections, particularly if evidence of renal dysfunction.
Infective endocarditis: The following recommendations are based on a consensus of

experts [3]. The full pediatric guidelines can be found here:
https://doi.org/10.1161/CIR.0000000000000298
Organism Directed Therapy

Organism First-Choice Alternative Choice
Streptococci
Highly susceptible to penicillin G (MBC 0.1 mcg/mL Penicillin G or Vancomycin or
or less); includes most viridans streptococci, CefTRIAXone First-generation
groups A, B, C, G nonenterococcal, group D cephalosporin or
streptococci (S bovis, S equinus) CefTRIAXone
Relatively resistant to penicillin (MBC 0.2 mcg/mL Penicillin G or Vancomycin +
or more); less-susceptible viridans streptococci Ampicillin + Gentamicin for
or Gentamicin (for first enterococci
enterococci 2 weeks, or entire Ampicillin +
course for CefTRIAXone (for
enterococci) aminoglycoside (AMG)-
resistant enterococci or
AMG-intolerant patient)
https://www.micromedexsolutions.com/micromedex2/librarian/CS/B56599/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
539
CefTRIAXone +
gentamicin (not for
enterococcal endocarditis)
Resistant to penicillin Consult an infectious ---
disease specialist.
Staphylococci (S aureus or coagulase-negative
staphylococci) †
Penicillin G Oxacillin or
Nafcillin or
Penicillin G susceptible (1 mcg/mL or less) (rare) First-generation
cephalosporin or
Vancomycin
Oxacillin or Vancomycin (for those

Nafcillin highly allergic to beta-
Penicillin G resistant (0.1 mcg/mL) with or without lactam antibiotics) or
Gentamicin First-generation
cephalosporin
Vancomycin Daptomycin for right-
Oxacillin (MRSA) resistant (4 mcg/mL) sided endocarditis, maybe
for left-sided
Vancomycin resistant or intolerant Daptomycin Unknown
†When prosthetic material present add riFAMpin
+ gentamicin (for first 2 weeks) for all
staphylococci
CefTAZidime or Broad-spectrum penicillin
Cefepime or Plus gentamicin (or
Cefotaxime or tobramycin or amikacin)
CefTRIAXone
Gram-negative enteric bacilli Plus gentamicin (or
tobramycin or
amikacin, depending
on susceptibility)
CefTRIAXone or Ampicillin (when
HACEK group Cefotaxime or susceptible)
Ampicillin-sulbactam Plus aminoglycoside
KEY: AMG = aminoglycosides; HACEK = Haemophilus species, Aggregatibacter species,
Cardiobacterium hominis, Eikenella corrodens, and Kingella species; MBC = minimum bactericidal
concentration, MRSA = methicillin-resistant Staphylococcus aureus (includes resistance to oxacillin,
nafcillin, and cephalosporins)
Baltimore, 2015
Administration
Intravenous: Dilute dose with sterile water for injection or NS to a concentration of 40

mg/mL and administer over 5 to 10 minutes or dilute to a concentration of 20 to 40 mg/mL
and infuse over 30 to 60 minutes [1][2].
MEDICATION SAFETY
540
Increase dosing interval in patients with hepatic dysfunction. Irritating to veins; watch for
phlebitis.
Adverse Effects
Cases of granulocytopenia have been reported.
D5W, D10W, and NS.
Acyclovir, aminophylline, atropine, chloramphenicol, cimetidine, dexamethasone, enalaprilat,

esmolol, famotidine, fentanyl, fluconazole, heparin, lidocaine, magnesium sulfate, morphine,
nicardipine, potassium chloride, propofol, sodium bicarbonate, tobramycin, and zidovudine.
Amikacin, aztreonam, gentamicin, hydrocortisone succinate, insulin, methylprednisolone,

midazolam, netilmicin, and vancomycin.
Monitoring
Observe IV site for signs of phlebitis and extravasation. Assess CBC, renal and hepatic
function weekly in patients receiving long-term therapy [2][4].
Pharmacology
Inhibits synthesis of bacterial cell wall. Better penetration into CSF than methicillin. Excreted
via hepatic clearance.
541
ABOUT
Available in 1 and 2-g vials. Reconstitute 1-g vial with 3.4 mL of sterile water for injection to
provide a final volume of 4 mL and a concentration of 250 mg/mL. Also available in 1-g in
50-mL and 2-g in 100-mL frozen single-dose bags. Thaw bags at room temperature or under
refrigeration. Do not force thaw by immersing into water baths or microwaving. pH of
resulting solution 6 to 8.5. Thawed solution stable for 3 days at room temperature, 21 days
refrigerator. Reconstituted solution stable for 3 days at room temperature, 7 days
refrigerated. Osmolality was determined to be 709 mOsm/kg of water. For direct intravenous
injection, dilute in 15 to 30 mL of NS.
542
Naloxone
Dose
Injection
Suggested dose: 0.1 mg/kg IV push.
Doses needed to reverse narcotic-induced depression may be as low as 0.01 mg/kg.
May give IM if adequate perfusion. Tracheal administration is not recommended.
There are no studies to support or refute the above dosing recommendations.
(Evzio(TM) auto-injector, 2 mg/0.4 mL concentration): 1 dose (2 mg) IM or subQ into

the anterolateral aspect of the thigh; may repeat every 2 to 3 minutes as needed using a
new auto-injector each time. If it is preferred to avoid abrupt precipitation of opioid
withdrawal symptoms, consider the use of an alternative naloxone product that can be
titrated to effect and can, where applicable, be dosed according to weight [1].
(Evzio(TM) auto-injector, 0.4 mg/0.4 mL concentration): 1 dose (0.4 mg) IM or subQ
into the anterolateral aspect of the thigh; may repeat every 2 to 3 minutes as needed using a
new auto-injector each time [2].
Nasal spray
Alternate naloxone-containing product may be preferable.
(Narcan® intranasal spray) Initial, 1 spray (2 or 4 mg) intranasally into 1 nostril. Use a
new nasal spray for subsequent doses and administer into alternating nostrils. May repeat
every 2 to 3 minutes. Higher or repeat doses may be required for patients taking partial
opioid agonists or mixed agonist/antagonists [3].
Uses
Narcotic antagonist Adjuvant therapy to customary resuscitation efforts for narcotic-

induced respiratory (CNS) depression. Naloxone is not recommended as part of the initial
resuscitation of newborns with respiratory depression in the delivery room. Before naloxone
is given, providers should restore heart rate and color by supporting ventilation [7]. The
American Heart Association (AHA) did not review the use of naloxone in the 2015 Neonatal
Resuscitation guidelines; therefore, the 2010 AHA guidelines still apply [8].

Injection: Indicated for complete or partial reversal of opioid depression, including
respiratory depression, induced by natural and synthetic opioids, and certain mixed agonist-
antagonist analgesics. Also indicated for diagnosis of suspected or known acute opioid
overdose [5].
Diagnosis of suspected or known acute opioid overdose [5].
IM/subQ Injection; Nasal Spray: Indicated for emergency treatment known or suspected
opioid overdose. It is intended for immediate administration as emergency therapy in setting
where opioids may be present [3][1].
In settings such as in neonates with known or suspected exposure to maternal opioid use,
when it may be preferable to avoid the abrupt precipitation of opioid withdrawal symptoms,
https://www.micromedexsolutions.com/micromedex2/librarian/CS/538F0E/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
543
consider use of an alternate-containing product that can be dosed according to weight and
titrated to effect. Also, in situations where the primary concern is for infants at risk for opioid
overdose, consider whether the availability of alternate naloxone-containing products may be
better suited than naloxone nasal spray [3]
Administration
IV Injection
Recommended route is IV push. IM or subQ administration is not recommended in children
due to erratic and unpredictable absorption. May also be given via intraosseous access for
emergent pediatric resuscitation [4][5].
IM or subQ Injection-Evzio(R)
Use the provided printed or electronic voice instruction for administration. If electronic voice
instruction does not operate, the dose can still be delivered [1].
Do not attempt to replace the red safety guard. Once removed, administer the dose
immediately or discard unused dose [1].
Administer IM into anterolateral aspect of the thigh. For children younger than 1 year, pinch
the thigh during administration. Immediately after administration, call for emergency help
and keep the patient under continuous surveillance [1].
Nasal route
Patient should be in a supine position for administration [6].
Do not prime or test the device prior to use [6].
Administer into alternate nostrils with each dose [6].
Do not reuse a Narcan(R) nasal spray, a new nasal spray must be used for each dose [6].
Turn patient onto their side after administration of the first dose [6].
MEDICATION SAFETY
May result in acute abstinence syndrome, manifested as convulsions, excessive crying, and
hyperactive reflexes. Opioid withdrawal may be life-threatening in neonates [2]. Recurrence
of respiratory and/or CNS depression may occur following an initial improvement in
symptoms [1].
Adverse Effects
No short-term toxicity observed. One case report of seizures secondary to acute opioid
withdrawal after administration to an infant born to an opioid abuser. Long-term safety has
not been investigated.
544
NS and D5W
Heparin, linezolid, and propofol.
Monitoring
Assess respiratory effort and neurologic status. Monitor patient for 24 hours for relapse [2]
[5].
Monitor for signs of acute withdrawal, including convulsion, excessive drying, and hyperactive
reflexes. Monitor blood pressure and ECG, and the development of pulmonary edema in
patients with pre-existing cardiac disease or use of medications having adverse
cardiovascular effects [2].
Pharmacology
Reverses respiratory depression by competing for CNS narcotic receptor sites. Onset of
action is variable, but usually within minutes after IV administration, and approximately 1
hour after IM administration. Half-life in neonates is approximately 70 minutes. Metabolized
by the liver and excreted in the urine. Increases circulating catecholamines.
Nasal administration of naloxone may be erratic or delayed [6].
ABOUT
Evzio™ Injection
Available as a 0.4 mg/0.4 mL or 2 mg/0.4 mL solution in a pre-filled single-dose, auto-
injector. Store in outer case until use. Temperature excursions permitted between 4 degrees
C and 40 degrees C (between 39 degrees and 104 degrees F) [1][2].
Narcan® Injections
Do not mix in an alkaline solution. Available in 0.4 mg/mL (1-mL fill in 2-mL Carpuject®
cartridge) and 1-mg/mL concentrations. Store at room temperature and protect from
light.
545
Narcan® nasal spray
Supplied as blister packages containing a single nasal spray cartridge (2- or 4-mg/0.1 mL
dose). Store at a controlled room temperature between 59 and 77 degrees F (15 and 25
degrees C), with excursions permitted between 4 and 40 degrees C (39 and 104 degrees F).
Protect from light. Do not freeze [3].
546
Neostigmine
Dose
Myasthenia gravis: 0.1 mg IM (give 30 minutes before feeding).

1 mg orally (give 2 hours before feeding). Dose may have to be increased and should be
titrated.
Reversal of neuromuscular blockade agent (NMBA): 0.03 to 0.07 mg/kg IV,

maximum total dose, 0.07 mg/kg; atropine or glycopyrrolate should be administered
prior to or concomitantly with neostigmine. The selection of the lower or higher dose range
depends on the extent of spontaneous recovery that has occurred at the time of
administration, the half-life of the NMBA being reversed, and whether there is a need to
rapidly reverse the NMBA [1]. Doses of atropine 0.02 mg/kg has been used.
Uses
Neonatal transient myasthenia gravis. Neonatal persistent (congenital) myasthenia gravis.

Reversal of neuromuscular blocking agents [1].
Administration
Administer IV over at least 1 minute [1]. Give with atropine or glycopyrrolate to prevent
possible bradycardia, increased salivation, and hyperperistalsis [2][2][3]. For myasthenia
gravis diagnosis, test dose is given IM [4][5].
MEDICATION SAFETY
Contraindicated in the presence of intestinal or urinary obstruction or in the presence of

peritonitis [1].
Precautions: Use cautiously in patients with bronchospasm, cardiac arrhythmia,

hypotension, or bradycardia [1][3]. Large doses may cause neuromuscular dysfunction in
patients with minimal blockade; dose reduction recommended if recovery from
neuromuscular blockade is nearly complete [1].
547
Adverse Effects
Adverse effects include muscle weakness, tremors, bradycardia, hypotension, respiratory

depression, bronchospasm, diarrhea, and excessive salivation [3].
No data.
Glycopyrrolate, heparin, hydrocortisone succinate, netilmicin, pentobarbital and potassium

chloride.
Monitoring
Monitor respiratory and cardiovascular status closely [3].

Train-of-four monitoring should used to evaluate recovery of neuromuscular blockade [1].
Pharmacology
Reversible quaternary cholinesterase inhibitor which inhibits acetylcholinesterase at the

neuromuscular junction, allowing accumulation of acetylcholine and thus restoring activity. In
1 study (n=27), ED50 (dose which produces 50% antagonism of neuromuscular blockade)
was 13.1 mcg/kg in infants and 15.5 mcg/kg in children. Protein binding (serum albumin) of
15% to 25%. Volume of distribution of approximately 0.5 L/kg in infants and children.
Undergoes hydrolysis by cholinesterase and also metabolized by microsomal enzymes in the
liver to 3-hydroxy-phenyl-trimethyl ammonium. Renal excretion accounts for 50% of drug
elimination. Half-life of approximately 30 to 60 minutes (shorter compared with adults) [3][6]
[7]. Reversal time dependent on neuromuscular blocker given and time of administration
(given at presence of intense neuromuscular blockade or delayed until recovery (first twitch
recovery of 1%, 10% or 25%)) [8].
ABOUT
548
Prostigmin®: Available as injectable solution in 10-mL multiple dose vials in concentrations of

1 mg/mL and 0.5 mg/mL. Protect from light[3].
Bloxiverz™: Available as injectable solution in 10-mL multiple dose vials in concentrations of
0.5 mg/mL and 1 mg/mL. Protect from light[1].
549
Netilmicin
Dose

Dosing Chart
PMA Postnatal Dose Interval
(weeks) (days) (mg/kg) (hours)
0 to 7 5 48
≤29* 8 to 28 4 36
≥29 4 24
0 to 7 4.5 36
30 to 34
≥8 4 24
≥35 ALL 4 24
* or significant asphyxia, PDA, or treatment with indomethacin
Uses
Treatment of infections caused by aerobic gram-negative bacilli (e.g. Pseudomonas,

Klebsiella, E coli
). Usually used in combination with a β-lactam antibiotic.
Administration
Give as an IV infusion by syringe pump over 30 minutes. Administer as a separate infusion

from penicillin-containing compounds. IM injection is associated with variable absorption,
especially in the very small infant.
MEDICATION SAFETY
Adverse Effects
Transient and reversible renal tubular dysfunction may occur, resulting in increased urinary
losses of sodium, calcium, and magnesium. Vestibular and auditory ototoxicity. The addition
of other nephrotoxic and/or ototoxic medications (e.g. furosemide, vancomycin) may
increase these adverse effects. Increased neuromuscular blockade (i.e. neuromuscular
550
weakness and respiratory failure) may occur when used with pancuronium or other
neuromuscular blocking agents and in patients with hypermagnesemia.
D5W, D10W, and NS.
Atropine, aztreonam, calcium gluconate, clindamycin, dexamethasone, heparin

(concentrations ≤1 unit/mL), hydrocortisone succinate, iron dextran, isoproterenol, linezolid,
metronidazole, norepinephrine, potassium chloride, procainamide, remifentanil, sodium
bicarbonate, and vitamin K1.
Ampicillin, furosemide, heparin (concentrations >1 unit/mL), mezlocillin, nafcillin, oxacillin,

penicillin G, propofol, and ticarcillin/clavulanate.
Monitoring
Measure serum concentrations when treating for more than 48 hours. Obtain peak
concentration 30 minutes after end of infusion, and trough concentration just prior to the
next dose. When treating patients with serious infections or significantly changing fluid or
renal status consider measuring the serum concentration 24 hours after a dose, and use the
chart below for the suggested dosing interval. Blood samples obtained to monitor serum drug
concentrations should be spun and refrigerated or frozen as soon as possible.
Therapeutic serum concentrations:

Peak: 5 to 12 mcg/mL (or Cmax /MIC ratio greater than 8:1)
Trough: 0.5 to 1 mcg/mL
24- hour Concentration

Suggested Dosing Intervals
Concentration at Suggested
Half-life
24 hours Dosing Interval
(hours)
(mg/L) (hours)
≤1 ~8 24
1.1 to 2.3 ~ 12 36
2.4 to 3.2 ~ 15 48
≥3.3 -- Measure level in 24 hours
551
Pharmacology
Dosing recommendations are based on: (1) Higher peak concentrations increase
concentration-dependent bacterial killing; (2) There is a post-antibiotic effect on bacterial
killing, especially when treating concurrently with a β-lactam antibiotic; (3) There may be
less toxicity with less frequent dosing, due to less renal drug accumulation. Volume of
distribution is increased and clearance is decreased in patients with PDA. Serum half-life is
prolonged in premature and asphyxiated newborns. Inactivation of netilmicin by penicillin-
containing compounds appears to be a time-, temperature-, and concentration-dependent
process. This is probably clinically significant only when penicillin-containing compounds are
mixed in IV solutions or when the blood is at room temperature for several hours before the
assay is performed.
ABOUT
Available in a concentration of 100 mg/mL in 1.5 mL vials. A 10 mg/mL dilution may be made
by adding 1 mL of this solution to 9 mL of sterile water for injection. Dilution is stable for 72
hours refrigerated. Do not freeze. No longer available in the US.
552
Nevirapine
Dose
Perinatal HIV Transmission, Prophylaxis:

Birth weight 1.5 to 2 kg: 8 mg/dose orally for 3 doses; give first dose within 48 hours of
birth (start as close to time of birth as possible, preferably within 6 to 12 hours of delivery),
second dose 48 hours after first dose, and third dose 96 hours after second dose. Must be
administered with zidovudine. This is the actual dose, not a mg/kg dose
[1].
Birth weight greater than 2 kg: 12 mg/dose orally for 3 doses; give first dose within 48
hours of birth (start as close to time of birth as possible, preferably within 6 to 12 hours of
delivery), second dose 48 hours after first dose, and third dose 96 hours after second dose.
Must be administered with zidovudine. This is the actual dose, not a mg/kg dose
[1].
HIV Infection, Treatment or Empiric Therapy

Investigational Doses
34 to 37 weeks gestation
0 to 7 days of age: 4 mg/kg/dose orally twice daily [1]
Older than 7 days : 6 mg/kg/dose orally twice daily [1]
Older than 4 weeks: 200 mg/m2 orally twice daily; option of 6 mg/kg/dose orally twice
daily for those being treated empirically [1]
37 weeks gestation or greater
Younger than 1 month: 6 mg/kg/dose orally twice daily [1].
Older than 4 weeks: 200 mg/m2 orally twice daily; option of 6 mg/kg/dose orally twice
daily for those being treated empirically [1]
Uses
Risk of HIV
in Newborn
Low risk of
transmission
to the regimen
Higher risk •Mother has not received antepartum •Dual ARV prophylaxis with 6 weeks zidovudine
of or intrapartum ARV therapy. and 3 doses of nevirapine (prophylaxis dosage,
transmission •Mother has received only with doses within 48 hours of birth, 48 hours
intrapartum ARV therapy later, and 96 hours after the second dose) OR
•Mother has received antepartum •Empiric therapy: zidovudine, lamiVUDine, and
and intrapartum ARV drugs but does treatment doses of nevirapine †† OR
not have viral suppression near • Empiric therapy: zidovudine, lamiVUDine, and
delivery, particularly with vaginal raltegravir ††
delivery
553
•Mother has acute or primary HIV
breastfeeding #
Confirmed
raltegravir)
KEY
delivery.
Prevention of maternal-fetal HIV transmission: . In a phase III randomized trial

(n=1684), the combination of 6 weeks of zidovudine plus 3 doses of nevirapine or the
combination of 6 weeks of zidovudine plus nelfinavir and lamiVUDine for 2 weeks was
associated with a lower intrapartum transmission rate when compared with zidovudine alone
in infants born to women who received no antenatal antiretroviral therapy (2.2% versus
2.5% versus 4.9%, respectively). The zidovudine/nelfinavir/lamiVUDine regimen was
associated with increased toxicity (eg, neutropenia) [3].
Pediatric FDA Approved Indication

Treatment of HIV-1 infection: in combination with other antiretroviral agents as either
immediate release tablets or suspension in pediatric patients 15 days or older [4] or
extended-release in patients 6 years or older with a body surface area of 1.17 m2 or greater
[5].
Administration
Can be given without regard to food [1].
The National Institute for Occupational Safety and Health (NIOSH) recommends the use of
single gloves by anyone handling intact tablets or capsules or administering from a unit-dose
package [2].
In the preparation of tablets or capsules, including cutting, crushing, or manipulating, or the
handling of uncoated tablets, NIOSH recommends the use of double gloves and a protective
gown. Prepare in a ventilated control device, if possible. Use respiratory protection if not
prepared in a control device. During administration, wear single gloves, and wear eye/face
protection if the formulation is hard to swallow or if the patient may resist, vomit, or spit up
[2].
NIOSH recommends the use of double gloves and a protective gown by anyone handling a
hazardous oral liquid or any hazardous drug via a feeding tube. Prepare in a control device, if
554
possible. Use respiratory, eye, and face protection if not done in a control device. During
administration, eye/face protection is needed if the patient may resist, or if there is potential
to vomit or spit up [2].
MEDICATION SAFETY
CONTRAINDICATIONS
Contraindicated in patients with moderate or severe hepatic impairment (Child Pugh Class
B or C, respectively) [4][7].
PRECAUTIONS
Hypersensitivity reactions, including severe rash, blisters, oral lesions, conjunctivitis, facial
edema, muscle or joint aches, general malaise, and significant hepatic abnormalities have
been reported. The risks of hepatic events or skin reactions are greatest in the first 6 weeks
of therapy. The hepatic events may occur at any time during therapy. Hepatic injury may
progress despite discontinuation of treatment [4][7]. Children with CD4 percentages greater
than 15% are at increased risk for hepatotoxicity and rash at initiation of nevirapine [1].
Immune reconstitution syndrome and fat redistribution may occur. Avoid concomitant use
with St. John's wort-containing products, efavirenz, atazanavir, fosamprenavir (without
ritonavir), boceprevir, telaprevir, or another non-nucleoside reverse transcriptase inhibitor [4]
[7].
Adverse Effects
Limited data on toxicity; none reported in neonates.
Common adverse events in children have been similar to those observed in adults (ie, rash,
fever, nausea, headache, diarrhea, abdominal pain, fatigue, and abnormal hepatic
transaminases). However, granulocytopenia was more common in children than adults [4]
[7]. Hepatotoxicity due to nevirapine appears to be less frequent in children than in adults
[1]. In pediatric clinical studies, rash has been reported in up to 27% of patients [8][4][9].
Neutropenia (9%), anemia (7%), and hepatotoxicity (2%) have also been reported in
children [7].
Black Box Warning
Severe, life-threatening, in some cases fatal, hepatotoxicity and skin reactions (eg, Stevens-
Johnson syndrome; toxic epidermal necrolysis; and hypersensitivity reactions characterized
by rash, constitutional findings, and organ dysfunction) have been reported. Women,
including pregnant women, and/or patients with higher CD4+ cell counts are at higher risk of
hepatotoxicity. Permanently discontinue nevirapine following severe hepatic, skin, or
hypersensitivity reactions. Monitor patients intensively during the first 18 weeks of therapy
with nevirapine to detect potentially life-threatening hepatotoxicity or skin reactions. Strictly
555
follow the 14-day lead-in period with immediate-release nevirapine 200 mg daily dosing [4]
[7] .
Monitoring
Initial Neonatal Management: Obtain a baseline CBC with differential; timing of followup
monitoring depends on numerous exposure risks. Recheck hemoglobin and neutrophil counts
4 weeks after initiation of prophylaxis for infants who receive combination
zidovudine/lamiVUDine-containing antiretroviral prophylaxis regimens [6].
Perform virologic test at baseline, 14 to 21 days of life, 1 to 2 months of age, and 4 to 6
months of age [1].
For nevirapine, frequent monitoring for hepatic toxicity, including liver function tests, during
the first 12 weeks of therapy is recommended[1].
Check transaminase levels immediately if a patient presents with signs or symptoms
indicative of hepatitis and/or a hypersensitivity reaction, or if patient develops rash within
first 18 weeks of nevirapine therapy. Permanently discontinue nevirapine in patients with
rash-associated transaminase elevations [4][7].
Pharmacology
Mechanism of Action: Nevirapine is a non-nucleoside antiretroviral agent that inhibits HIV-

1 replication by selectively interfering with viral reverse transcriptase without requiring
intracellular metabolism. It also inactivates cell-free virions in the genital tract and breast
milk. Synergistic antiviral activity occurs when administered with zidovudine [7].
Absorption: Nevirapine is rapidly absorbed after oral administration to pregnant women [7]
[10].
Concentrations: The 3-dose nevirapine regimen in neonates for prevention of perinatal HIV
transmission provided serum concentrations above 100 nanograms (ng)/mL in all newborns
through 10 days of life [11].
All nevirapine concentrations, mostly sampled within the first 28 days of dosing, were greater
than 100 ng/mL in 116 preterm infants (mean gestational age, 31.5 weeks; median birth
weight, 1310 g) administered 2 mg/kg/d orally for 14 days, then 4 mg/kg/day thereafter.
Median nevirapine concentrations were 4200 ng/mL before 14 days and 2300 ng/mL after 14
days (p less than 0.0001). Concentrations greater than 10,000 ng/mL were observed in 6
infants at less than 15 days of age; no adverse reactions were reported [12].
In preterm infants (28 to 37 weeks of gestation) nevirapine plasma concentrations, 8 days
after birth, were greater than 100 ng/mL in 78% of infants whose mothers had received
nevirapine immediately during labor and 70% in infants whose mothers had not received
nevirapine during labor (p=0.49). Within 1 hour after birth, infants received a single-dose of
oral nevirapine 2 mg/kg for infants less than 2 kg and 6 mg for infants greater than 2 kg
[13].
Cmax: The median (range) Cmax was 1438 ng/mL (350 to 3832 ng/mL) and 1535 ng/mL
(635 to 4218 ng/mL) for infants (n=58) whose mothers had received nevirapine during labor
and in infants (n=23) whose mothers had not received nevirapine during labor, respectively.
The preterm infants (range, 28 to 37 weeks gestation), within 1 hour after birth, received a
single-dose of oral nevirapine 2 mg/kg for infants less than 2 kg and 6 mg for infants greater
556
than 2 kg [13].
Tmax: The median (range) Tmax was 25 hours 50 minutes (9 hours 40 minutes to 83 hours
45 minutes) and 17 hours 35 minutes (7 hours 40 minutes to 29 hours) for infants (n=58)
whose mothers had received nevirapine during labor and in infants (n=23) whose mothers
had not received nevirapine during labor, respectively. The preterm infants (range, 28 to 37
weeks gestation), within 1 hour after birth, received a single-dose of oral nevirapine 2 mg/kg
for infants less than 2 kg and 6 mg for infants greater than 2 kg [13].
AUC: The median (range) AUC was 174,134 ngXhr/mL (22,308 to 546,408) and 168,576
ngXhr/mL (20,268 to 476,712) for infants (n=58) whose mothers had received nevirapine
during labor and in infants (n=23) whose mothers had not received nevirapine during labor,
respectively. In small for gestational age infants (n=8), nevirapine AUC was significantly
higher compared with appropriate for gestational age infants (n=15). The preterm infants
(range, 28 to 37 weeks gestation), within 1 hour after birth, received a single-dose of oral
nevirapine 2 mg/kg for infants less than 2 kg and 6 mg for infants greater than 2 kg [13].
Distribution: After oral administration to pregnant women, nevirapine is highly lipophilic,

resulting in therapeutic concentrations being readily transferred across the placenta to the
fetus [7][10].
Vd: The Vd was 1.703 L (0.624 to 6.19 L) in 23 preterm infants (24 to 37 weeks gestation)
[13].
Metabolism: Nevirapine is extensively metabolized by, and an inducer of, hepatic CYP3A4
and CYP2B6 isoenzymes. Concomitant administration of phenobarbital or phenytoin (CYP3A
inducers) may affect plasma concentrations [4].
Excretion
Clearance: The clearance was 34.91 mL/hr (6.2 to 163.79 ml/hr) in 23 preterm infants (24
to 37 weeks gestation). In small for gestational age infants (n=8), nevirapine clearance was
significantly lower compared with appropriate for gestational age infants (n=15) after a
single-dose of oral nevirapine 2 mg/kg for infants less than 2 kg and 6 mg for infants greater
than 2 kg [13].
Half-life:
Serum half-life in neonates is approximately 30 to 44 hours [7][10].
Preterm Infants: The median (range) half-life was 59 hours (15.4 to 532.6 hours) and 69
hours (22.12 to 172.26 hours) for infants (n=58) whose mothers had received nevirapine
during labor and in infants (n=23) whose mothers had not received nevirapine during labor,
respectively [13].
ABOUT
Available: Oral suspension 10 mg/mL.

Storage: Store at room temperature. Shake suspension gently prior to administration [4].
557
NiCARdipine
Dose
Initial dose: 0.5 mcg/kg per minute continuous IV infusion.

Titrate dose to response. Blood pressure will begin to decrease within minutes of starting the
infusion, reaching half of its ultimate decrease in approximately 45 minutes. Blood pressure
equilibrium will not be achieved for approximately 50 hours (adult data).
Maintenance doses are usually 0.5 to 2 mcg/kg per minute.
Uses
Acute severe hypertension [4]
Nicardipine reduced blood pressure in neonatal patients experiencing hypertension while on

extracorporeal membrane oxygenation (ECMO) without hypotensive episodes in a
retrospective review of 8 neonates (median gestational age, 36.5 weeks; interquartile range,
35.3 to 38 weeks). The mean starting dose was 0.52 (+/- 0.22) mcg/kg/min and titrated to a
maximum rate of 1.1 (+/- 0.85) mcg/kg/min (range, 0.3 to 3 mcg/kg/min) for a median
duration of 51 hours (range, 4 to 227 hours) [4].
Administration
Intravenous: Dilute prior to administration to a concentration of 0.1 mg/mL or use

premixed solution (0.1 mg/mL; 200 mL). Administer by a central line or large peripheral vein
[1]. There are literature reports of higher concentrations being used (0.5 mg/mL) in children
without significant problems, except for superficial phlebitis [2][3].
MEDICATION SAFETY
Contraindicated in patients with advanced aortic stenosis [1].
Adverse Effects
558
No adverse effects have been reported in neonates (small numbers). Hypotension and
tachycardia are dose-dependent in adults. Headache, nausea, and vomiting were the other
common effects reported.
D5W, NS, and D5NS.
LR.
Amikacin, aminophylline, aztreonam, calcium gluconate, cefazolin, ceftizoxime,

chloramphenicol, cimetidine, clindamycin, dobutamine, dopamine, enalaprilat, epinephrine,
erythromycin lactobionate, esmolol, famotidine, fentanyl, gentamicin, heparin (concentrations
of 1 unit/mL or less), hydrocortisone, lidocaine, linezolid, lorazepam, magnesium sulfate,
metronidazole, midazolam, milrinone, morphine, nafcillin, nitroglycerin, norepinephrine,
penicillin G potassium, piperacillin, potassium chloride, potassium phosphate, ranitidine,
sodium acetate, sodium nitroprusside, tobramycin, trimethoprim/sulfamethoxazole,
vancomycin, and vecuronium.
Ampicillin, cefepime, cefoperazone, ceftazidime, furosemide, heparin (concentrations greater

than 1 unit/mL), micafungin, sodium bicarbonate and thiopental.
Monitoring
Continuous monitoring of blood pressure, heart rate and rhythm during initiation of therapy,
and frequently thereafter. Observe IV site for signs of irritation.
Pharmacology
559
niCARdipine is a dihydropyridine calcium channel blocker that significantly decreases systemic
vascular resistance. Unlike other calcium channel blockers, it has limited effects on the
myocardium. It is extensively metabolized by the liver, and is highly protein bound. Following
infusion in adults, niCARdipine plasma concentrations decline tri-exponentially, with a rapid
early distribution phase (alpha half-life of 2.7 minutes), an intermediate phase (beta half-life
of 44.8 minutes), and a slow terminal phase (gamma half-life of 14.4 hours) that can only be
detected after long-term infusions. Experience in neonates is limited, and there are no
reported pharmacokinetic data.
ABOUT
Available as 2.5-mg/mL solution for injection in 10-mL ampules. Dilute prior to

administration to a concentration of 0.1 mg/mL. Dilution is stable at room
temperature for 24 hours. Also available as premixed solution (0.1 mg/mL, 0.2 mg/mL; 200
mL) in dextrose or sodium chloride. Store ampuls and premixed solution at controlled room
temperature in carton until ready to use. Freezing does not adversely affect the product, but
exposure to elevated temperatures should be avoided. Protect from light.
560
Nitric Oxide
Dose
Greater than 34 weeks gestation

20 ppm. Manufacturer recommends treatment up to 14 days or until underlying oxygen
desaturation has resolved and the neonate can be weaned from nitric oxide therapy. MAX
20 ppm [1][2][3].
If within 4 hours PaO2 increases to at least 60 torr, decrease to 5 ppm. Continue at 5 ppm
and wean fiO2 as tolerated. When fiO2 is less than 0.6 and ventilatory support has been
decreased, wean nitric oxide in 1 ppm increments at approximately 4 hour intervals as
tolerated. Discontinue when stable on 1 ppm for 4 hours. The usual length of treatment is
less than 4 days. Infants who cannot be weaned off after 4 days should undergo further
diagnostic testing for other diseases.
Uses
Bronchopulmonary dysplasia, prevention (premature newborn): Inhaled nitric oxide

is not recommended for premature newborns for the prevention of bronchopulmonary
dysplasia [5]. No differences were demonstrated in mortality, incidence of bronchopulmonary
dysplasia, or respiratory or neurodevelopmental outcomes in very preterm infants (younger
than 30 weeks' gestation and less than 1250 g) at 36 weeks through 24 months'
postmenstrual age in a randomized trial (n=451) comparing inhaled nitric oxide and placebo
initiated on postnatal days 5 to 14 and continued for 24 days [6].
Persistent pulmonary hypertension (PPHN)

Full-term newborn: Inhaled nitric oxide in term and near-term infants with PPHN or
hypoxemic respiratory failure and an oxygenation index of greater than 25 reduces the need
for extracorporeal membrane oxygenation. [7].
Preterm newborn: Based on the established safety profile with short and long follow-up
durations [5], inhaled nitric oxide can be beneficial for preterm infants with severe
hypoxemia, which is primarily due to PPHN rather than parenchymal lung disease,
particularly if associated with prolonged rupture of membranes and oligohydramnios. [5][7].
A subgroup analysis of preterm infants with pulmonary hypertension did not support the use
of inhaled nitric oxide during a meta-analysis of preterm infants (less than 34 weeks
gestational age) on respiratory support [8].
Respiratory failure: Available evidence does not support the use in preterm infants less
than 34 weeks GA [8]. This was confirmed in a multicenter, randomized, double-blind study
of preterm infants born at less than 29 weeks gestation with moderate respiratory failure.
Treatment was initiated within 24 hours of life with inhaled nitric oxide (5 ppm) or placebo
and continued for 7 to 21 days. The survival (without bronchopulmonary dysplasia) rate at
36 weeks postmenstrual age was 65% vs 66%, respectively. At 2 years follow-up, there was
no difference in growth, neurologic development, including cerebral palsy, or respiratory
outcomes between the nitric oxide group and placebo group [9]. The use of iNO in this
https://www.micromedexsolutions.com/micromedex2/librarian/CS/9B7670/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
561
population should be done under the auspices of a research protocol.
Low-dose inhaled nitric oxide (adjusted to 5 to 20 parts per million (ppm)) significantly
reduced the use of extracorporeal membrane oxygenation (ECMO) compared with 100%
nitrogen (38% vs 64%) in infants with persistent pulmonary hypertension and hypoxic
respiratory failure in the randomized CINRGI trial (N=248). Overall, there was no significant
difference in mortality (10 vs 13 infants), ventilator settings, heart rate, mean blood
pressure, or level of dopamine support during the first 4 hours. After 1 hour of therapy, the
ratio of arterial to alveolar oxygen was significantly increased in the nitric oxide group (0.1 vs
0.05). Among surviving infants, the incidence of chronic lung disease at 30 days was
significantly lower in the nitric oxide group (7% vs 20%). The study gas was initiated at 20
ppm and continued for 4 hours then subsequently decreased to 5 ppm based on clinical
stability within the first 24 hours, or after 24 hours of treatment in all infants [10].
In a retrospective analysis of the CINRGI study, among the 66 responders in the nitric oxide
group (those who did not need ECMO), 48 patients responded within 30 minutes of therapy
initiation, 6 patients within 1 hour, 8 within 24 hours, and 4 after 24 hours. Among the 48
nonresponders in the nitric oxide group (those who went on to need ECMO), 40 initially
responded to therapy (22 within 30 minutes, 7 within 1 hour, 1 within 24 hours, and 10 after
24 hours) by having a 10% or more increase in PaO(2) or a 10% or greater decrease in
oxygenation index, which was similar to the responding group, even though nonresponders
went on to need ECMO. Of the 29 nonresponders who initially showed a response to nitric
oxide therapy, PaO(2) levels at baseline were significantly lower than responders (46 vs 88
mm Hg). Among patients in the control group who responded (n=38), 20 responded within
30 minutes, 6 within 1 hour, and 11 within 24 hours, and 1 after 24 hours. Overall, disease
severity at baseline did not correspond to time to improvement in oxygenation [11].

Treatment of term and near-term infants (greater than 34 weeks gestation) with hypoxic
respiratory failure associated with clinical or echocardiographic evidence of pulmonary
hypertension in conjunction with ventilatory support or other appropriate agents [1][3].
Administration
Genosyl®
• Administer using a calibrated Genosyl® Delivery System [1].
• Only validated ventilator systems should be used. Keep available a backup power supply to
address power failures [1].
• The delivery system consists of a primary system and a fully functional second system that
can be used as backup. The delivery system monitors the concentration of nitric oxide,
nitrogen dioxide and air; system will shutdown if nitrogen dioxide reaches 3 parts per million
(ppm) [1].
• The delivery system must be used with antioxidant cartridges not older than 12 months
from the manufacturing date [1].
INOmax®
Must be administered using a calibrated FDA-cleared nitric oxide delivery system (NODS);
refer to NODS labeling to determine which NODS to use. When using a NODS specifically
cleared for use in the MRI suite, only use INOmax MR Conditional cylinders at 100 gauss or
less [4].
Keep backup battery power supply and independent reserve nitric oxide delivery system on
standby [3].
562
Noxivent 102™
Use equipment rated for cylinder pressure [2].
MEDICATION SAFETY
Contraindications
Contraindicated in infants dependent on right-to-left cardiac blood flow [4].
Precautions
Cardiovascular: Pulmonary edema, increased pulmonary capillary wedge pressure,
worsening of left ventricular dysfunction, systemic hypotension, bradycardia, and cardiac
arrest may occur in patients with left ventricular dysfunction; discontinue if occurs [4]
Hematologic: Dose-related methemoglobinemia may occur and lead to hypoxemia;
monitoring recommended and dosage adjustment may be necessary [4]
Respiratory: Abrupt discontinuation may worsen oxygenation and increase pulmonary
artery pressure (rebound pulmonary hypertension syndrome); carefully taper dose during
weaning; monitoring recommended; restart treatment immediately if rebound pulmonary
hypertension occurs [4]
Respiratory: The risks of methemoglobinemia and elevated NO2 levels increase significantly
at doses greater than 20 ppm. Methemoglobin has very high affinity for oxygen and has a
profound effect on oxygen content. Small increases in methemoglobin cause significant
decreases in available oxygen content. Normal methemoglobin levels are less than 1%. In
most neonatal studies, methemoglobinemia was defined as levels of 5% to 7%. Cyanosis
develops at levels of 10%, although the patients generally remain asymptomatic. At
methemoglobin levels approaching 30%, patients begin to experience respiratory distress,
and cardiac, gastrointestinal, and neurologic symptoms. A methemoglobin level greater than
50% is usually lethal. Avoid concomitant use of acetaminophen, metoclopramide, sulfa
drugs, topical anesthetics (EMLA, benzocaine, lidocaine, prilocaine). Congenital deficiencies in
the methemoglobin reductase enzyme system occur but are rare. The environmental
exposure limit set by the Occupational Safety and Health Administration is 25 ppm for NO
and 5 ppm for NO2[17].
Respiratory: Airway injury from elevated nitrogen dioxide levels may occur; monitoring
recommended and dosage adjustment may be necessary [4]
Monitoring
Measure blood methemoglobin concentration 4 to 8 hours after initiation of therapy and

periodically thereafter [1][12] .
Monitor inspired PaO2 and nitrogen dioxide (NO2) throughout administration of therapy [1]
[3].
Assess delivery system if there is an unexpected change in NO2 concentration or if the NO2
concentration reaches 0.5 ppm (Glenosyl®) [1] or 3 ppm (Inomax®) [3] when measured in
the breathing circuit [1][3].
During weaning and discontinuation from therapy, monitor for hypoxemia [1][3].
Continuous monitoring of oxygenation, blood pressure and heart rate are mandatory [13]
563
[14][15][16].
Pharmacology
Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that decreases extrapulmonary
right-to-left shunting. It activates guanylate cyclase by binding to its heme component
leading to production of cyclic GMP, with subsequent relaxation of pulmonary vascular
smooth muscle. Oxygenation is also improved due to the redirecting of blood from poorly
aerated to better aerated distal air spaces. In addition, iNO appears to have both antioxidant
and antiinflammatory activities. Systemically absorbed after inhalation. Metabolized to nitrate
which is excreted in the urine [12][13].
ABOUT
INOmax®
Nitric oxide for inhalation is supplied in medical grade gas cylinders in 800 ppm
concentrations. Store at room temperature [3].
Complete comprehensive periodic training program for Nitric Oxide Delivery Systems [3].
Genosyl®
Availability: Delivery system cassettes with at least 216 L of 800 ppm nitric oxide gas (at
standard temperature and pressure) [1]
Storage: Store at a controlled room temperature between 20 and 25 degrees C (68 and 77
degrees F), with excursions permitted between 15 and 30 degrees C (59 and 86 degrees F)
[1].
564
Norepinephrine
Dose
Septic Shock
Gestational age greater than 35 weeks: Initial dose, 0.2 to 0.5 mcg/kg/min by IV
infusion; titrate every 30 minutes to target blood pressure. Usual Infusion rate 0.2 to 2
mcg/kg/min; higher rates may be required [1].
Uses
Severe Sepsis and Septic Shock[3][6]
Hemodynamic Support - First 60 Minutes

Time Management- Proceed to next step if shock persists
0
Maintain airway and establish access
minutes
Push 10 mL/kg isotonic crystalloid or colloid boluses up to 40 mL/kg until improved
5
perfusion or unless hepatomegaly.
minutes
Begin prostaglandin infusion until rule out ductal-dependent lesion.
15 DOPamine less than 10 mcg/kg/min +/- DOBUTamine for fluid-refractory shock
minutes EPINEPHrine 0.05 to 0.3 mcg/kg/min for fluid-refractory DOPamine-resistant shock
Cold shock-Poor LV function Add nitrovasodilator milrinone or inamrinone
Normal blood pressure with volume loading
ScvO(2) less than 70%*/Hgb greater than
12 g/dL
than 3.3 L/min/m(2)
Cold shock- Poor RV function Inhaled nitric oxide
PPHN Inhaled iloprost or IV adenosine
ScvO(2) less than 70%* IV milrinone or inamrinone
60 min than 3.3 L/min/m(2)
Titrate volume
Warm shock- Low blood pressure Add norepinephrine
Vasopressin or terlipressin or angiotensin
Hydrocortisone if absolute adrenal
insufficiency.
Triiodothyronine if hypothyroid.
Refractory shock
Begin pentoxifylline if VLBW newborn.
Consider closing PDA if hemodynamically
significant.
ECMO
Goals
•First Hour: restore and maintain heart rate thresholds, capillary refill of 2 seconds or less, and
normal blood pressure.
565
• NICU: normal MAP-CVP, preductal and postductal oxygen saturation difference less than 5%,
*ScvO(2) greater than 70% (except congenital heart patients with mixing lesions), SVC flow greater
than 40 mL/kg/min, or cardiac index greater than 3.3 L/min/m(2)
KEY: CI = cardiac index, Hgb = hemoglobin, LV function = left ventricle function, MAP-CVP = mean
arterial pressure-central venous pressure, PDA = patent ductus arteriosus, PPHN = persistent
pulmonary hypertension of the newborn, ScvO(2) = continuous central venous oxygen saturation,
SVC = superior vena cava, VLBW = very low birth weight
Davis et al: Crit Care Med 2017;45(6)
A small observational study (n=22; gestational age greater than 35 weeks) suggested that
norepinephrine be used for shock associated with hypotension and poor perfusion (cold
shock) that has not responded to fluid therapy and dopamine/dobutamine. Norepinephrine
was started via central venous catheter at 0.2 to 0.5 mcg/kg/min and titrated every 30
minutes to target mean blood pressure; maximum individual infusion rate was 7.1
mcg/kg/min. Mean values for systemic blood pressure (diastolic greater than systolic), heart
rate, and urine output increased, while oxygen need and plasma lactate levels decreased.
Three infants required extracorporeal membrane oxygenation due to persistent pulmonary
hypertension. The mortality rate was 18% [1].
Persistent pulmonary hypertension (PPHN) with circulatory failure. A small

observational study (n=18; gestational age greater than 35 weeks) demonstrated that
norepinephrine improved lung function in neonates with PPHN having low systemic blood
pressure and reduced cardiac output despite fluid resuscitation. Norepinephrine was started
via central venous catheter at 0.5 mcg/kg/min and titrated every 30 minutes to target
systemic artery pressure (SAP); the maximum infusion rate was 1 mcg/kg/min. Mean SAP
and mean pulmonary artery pressure (PAP) were both increased, with a concomitant
decrease in the mean PAP/SAP ratio, resulting in increased pulmonary blood flow and cardiac
output. In addition, median oxygen need was progressively reduced over time. No study
patient required extracorporeal membrane oxygenation [4].
Administration
Must be diluted before infusion and administered via large peripheral vein
(antecubital or femoral) [2]. Preferred route is umbilical arterial and venous catheter.
Intraosseous route is an option, but is not preferred especially in preterm newborns [3][1][4]
at a concentration of 16 to 100 mcg/mL [5][1][4]. Avoid the catheter tie-in technique.
Constantly watch the flow rate and never leave patient unattended [2].
MEDICATION SAFETY
Contraindicated in hypotension due to blood volume deficits (except in emergency until

blood can be administered), mesenteric or peripheral vascular thrombosis, during
cyclopropane and halothane anesthesia, and in presence of profound hypoxia or hypercarbia
[2].
Contains sodium metabisulfite, which may cause allergic-type reactions (eg, anaphylactic
566
symptoms; life-threatening or less severe asthmatic episodes) in certain susceptible people.
Sensitivity is more common in asthmatic than nonasthmatic patients [2].
Avoid abrupt withdrawal; taper infusion gradually, as indicated [2].
Black Box Warning
To prevent sloughing and necrosis in areas in which extravasation has taken place, the area
should be infiltrated as soon as possible with saline solution containing phentolamine
mesylate 1 to 5 mg diluted in 5 mL of normal saline, an adrenergic blocking agent [3].
Synthetic blockade with phentolamine causes immediate and conspicuous local hyperemic
changes if the area is infiltrated within 12 hours. Phentolamine should be given as soon as
possible after the extravasation is noted. A syringe with a fine hypodermic needle should be
used, with the solution being infiltrated liberally throughout the area, which is easily
identified by its cold, hard, and pallid appearance [2].
D5W, D5NS, NS, LR
Norepinephrine 0.004 mg/mL:

Famotidine 0.2 mg/mL, vasopressin 0.2 units/mL, 20 units/10 mL, and 40 units/10 mL.

Propofol 10 mg/mL, vasopressin 0.2 units/mL.

Clonidine 0.018 mg/mL.

Dobutamine 2 mg/mL, dopamine 3.2 mg/mL, epinephrine 0.008 mg/mL.

Dopamine 3.2 mg/mL, esmolol 40 mg/mL, labetalol 5 mg/mL, midazolam 1 mg/mL, milrinone
0.4 mg/mL, morphine 1 mg/mL.

Dobutamine 10 mg/mL.

Bivalirudin 5 mg/mL, cisatracurium 0.1, 2, and 5 mg/mL, dexmedetomidine 4 mcg/mL,
diltiazem 1 mg/mL.
567
Argatroban 1 mg/mL, caspofungin 0.5 and 0.7 mg/mL, daptomycin 10 mg/mL, diltiazem 1
mg/mL, dobutamine 4 mg/mL, dopamine 3.2 mg/mL, epinephrine 0.02 mg/mL, ertapenem
20 mg/mL, fentanyl citrate 50 mcg/mL, granisetron 50 mcg/mL, heparin 100 units/mL,
hydromorphone 1 mg/mL, labetalol 2 mg/mL, linezolid 2 mg/mL, lorazepam 0.5 mg/mL,
methotrexate 15 mg/mL, metronidazole 5 mg/mL, micafungin 1.5 mg/mL, midazolam 2
mg/mL, milrinone 0.2 mg/mL, morphine 2 mg/mL, mycophenolate mofetil 6 mg/mL,
nicardipine 1 mg/mL, nitroglycerin 0.4 mg/mL, octreotide acetate 5 mcg/mL, ondansetron 1
mg/mL, palonosetron 50 mcg/mL, pancuronium 0.1 mg/mL, piperacillin/tazobactam 40 and 5
mg/mL, ranitidine 1 mg/mL, tacrolimus 20 mcg/mL, vecuronium 1 mg/mL, voriconazole 4
mg/mL.

Amikacin 20 mg/mL, atracurium 5 mg/mL, atropine 0.5 mg/mL, aztreonam 80 mg/mL,
bumetanide 0.125 mg/mL, calcium chloride 50 mg/mL, calcium gluconate 50 mg/mL,
cefazolin 220 mg/mL, cefotaxime 285 mg/mL, cefotetan 400 mg/mL, cefoxitin 450 mg/mL,
ceftazidime 400 mg/mL, ceftriaxone 165 mg/mL, cefuroxime 125 mg/mL, chloramphenicol
333 mg/mL, cimetidine 24 mg/mL, clindamycin 48 mg/mL, cyanocobalamin 0.5 mg/mL,
cyclosporine 2 mg/mL, dexamethasone 12 mg/mL, digoxin 0.125 mg/mL, diphenhydramine
25 mg/mL, dobutamine 6.25 and 10 mg/mL, dopamine 12.8 mg/mL, doxycycline 4 mg/mL,
enalaprilat 0.625 mg/mL, ephedrine 12.5 mg/mL, epinephrine 0.5 mg/mL, epoetin alfa 5000
units/mL, erythromycin 20 mg/mL, esmolol 40 mg/mL, famotidine 5 mg/mL, fentanyl 25
mcg/mL, fluconazole 2 mg/mL, gentamicin 6.4 mg/mL, glycopyrrolate 0.1 mg/mL, heparin
160 units/mL, hydrocortisone 62.5 mg/mL, imipenem/cilastatin 5 mg/mL, isoproterenol 80
mcg/mL, ketorolac 15 mg/mL, labetalol 2.5 mg/mL, lidocaine 10 mg/mL, magnesium 250
mg/mL, mannitol 150 mg/mL (15%), methyldopate 25 mg/mL, methylprednisolone 125
mg/mL, metoclopramide 2.5 mg/mL, metoprolol 0.5 mg/mL, midazolam 2.5 mg/mL,
morphine 4 mg/mL, nafcillin 250 mg/mL, nalbuphine 10 mg/mL, naloxone 16 mcg/mL,
netilmicin 50 mg/mL, nitroglycerin 1.6 mg/mL, ondansetron 1 mg/mL, oxacillin 160 mg/mL,
papaverine 15 mg/mL, penicillin G potassium 500,000 units/mL, penicillin G sodium 500,000
units/mL, phentolamine 5 mg/mL, phenylephrine 4 mg/mL, piperacillin 320 mg/mL,
potassium chloride 1 mEq/mL, procainamide 250 mg/mL, prochlorperazine 2.5 mg/mL,
propranolol 0.5 mg/mL, protamine 5 mg/mL, pyridoxine 50 mg/mL, ranitidine 2 mg/mL,
succinylcholine 8 mg/mL, ticarcillin/clavulanate 195 mg/mL, tobramycin 6.4 mg/mL,
vancomycin 20 mg/mL, vasopressin 4 units/mL, verapamil 1.25 mg/mL.
Norepinephrine 1 mg/mL:
Argatroban 1 mg/mL, dobutamine 10 mg/mL, epinephrine 0.5 and 1 mg/mL, heparin 1
unit/mL, hydrocortisone 0.01 mg/mL, meropenem 1 and 50 mg/mL, mycophenolate mofetil
5.9 mg/mL, potassium chloride 0.04 mEq/mL, propofol 10 mg/mL.
Aminophylline, amphotericin B conventional colloidal, amphotericin B lipid complex,

azathioprine, diazepam, diazoxide, foscarnet, ganciclovir, indomethacin, pentobarbital,
phenobarbital, phenytoin, sodium bicarbonate, sulfamethoxazole/trimethoprim.
Compatibility information refers to physical compatibility and is derived from Trissel’s™ 2

Clinical Pharmaceutics Database. The determination of compatibility is based on
concentrations for administration recommended herein. Drug compatibility is dependent on
multiple factors (eg, drug concentrations, diluents, storage conditions). This list should not
568
be viewed as all-inclusive and should not replace sound clinical judgment. The user is
referred to Trissel’s™ 2 for more complete details.
Trissel’s™ 2 Clinical Pharmaceutics Database, version updated on 12/15/2012.
Monitoring
Monitor blood pressure every 2 minutes from start of administration until target blood
pressure is obtained and every 5 minutes thereafter until infusion is discontinued. Observe
for signs of extravasation. Assess for plasma volume depletion during prolonged treatment
[2]. When used for septic shock, monitor hemodynamics and oxygen saturation using
techniques appropriate for clinical status. Target heart rate and perfusion pressure
appropriate for patient's gestational and postnatal age. For a full-term newborn, the target
heart rate and perfusion pressure (mean arterial pressure minus central venous pressure) are
110 to 160 beats/min and 55 mm Hg, respectively [3].
Pharmacology
Norepinephrine, a sympathomimetic amine, has both alpha-adrenergic activity resulting in

peripheral vasoconstriction, and beta-adrenergic activity leading to inotropic stimulation of
the heart and coronary artery vasodilation [2].
ABOUT
Available for IV infusion in 4-mL ampules containing 1 mg/mL. Protect ampules from light
[2].
Mix norepinephrine in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since

dextrose-containing solutions protect against excessive oxidation and subsequent potency
loss Administration in saline alone is not recommended[2]. Final concentration of 100
mcg/mL [1][4]
569
Nystatin
Dose
Oral
Oral Candidiasis
Infants: 2 mL (200,000 units) orally 4 times/day; use dropper to place one-half of the dose
in each side of mouth and avoid feeding for 5 to 10 minutes. Continue treatment for at least
48 hours after perioral symptoms disappear and cultures demonstrate eradication of Candida
albicans [1]
Premature and low birth weight Infants: 1 mL (200,000 units) orally 4 times/day; use
dropper to place one-half of the dose in each side of mouth and avoid feeding for 5 to 10
minutes. Continue treatment for at least 48 hours after perioral symptoms disappear and
cultures demonstrate eradication of Candida albicans [1]
Oral
Invasive Candidiasis; Prophylaxis (birth weight less than 1500 g): 1 mL of 100,000
units/mL suspension orally 3 times per day for 6 weeks in neonatal intensive care unit (with
greater than 10% rate of invasive candidiasis)[2].
Topical: Apply ointment or cream to affected area every 6 hours.

Continue treatment for 3 days after symptoms have subsided.
Uses
Treatment of mucocutaneous candidal infections. Prophylaxis against invasive fungal

infections in high risk VLBW infants.
Neonatal Candidiasis[2]
Invasive candidiasis and candidemia, or very low-birth weigh infants with asymptomatic
candiduria .
Fluconazole IV or oral is an alternative for those who have not been receiving
prophylaxis with fluconazole.
Lipid formulation amphotericin B agent is an alternative; however use with caution,
especially in the presence of urinary tract involvement.
Echinocandins (caspofungin, anidulafungin, or micafungin) should be limited to salvage
therapy or scenarios of resistance or toxicity to amphotericin B deoxycholate or
fluconazole
Central nervous system infections

Liposomal amphotericin B agent is an alternative.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/A62C09/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
570
Salvage therapy with flucytosine may be added in those patients who have not
responded to initial therapy.
Fluconazole may be used as step-down therapy for those patients with fluconazole-
susceptible isolates who respond to initial therapy
Neonatal intensive care unit (with greater than 10% rate of invasive candidiasis)
Prophylaxis with IV or oral fluconazole for 6 weeks is recommended for neonates with
birth weights of less than 1000 g
Prophylaxis with oral nystatin is an alternative in neonates with birth weights of less
than 1500 g when fluconazole is unavailable or fluconazole resistance is present

Treatment of candidiasis in the oral cavity (oral suspension). Limited clinical studies in
premature and low birth weight infants indicate that 1 mL four times daily is effective.[1].
Administration
•Shake well before use [1].

•Use dropper to place one-half of the dose in each side of mouth and avoid feeding for 5 to
10 minutes [1].
MEDICATION SAFETY
Adverse Effects
Possible skin rash caused by vehicle in ointment/cream.
Monitoring
Assess response to drug.
Pharmacology
Polyene antifungal similar in structure to amphotericin B. May be fungicidal or fungistatic.

Binds to the fungal cell membrane causing disruption of the cell structure. Not absorbed well
from the GI tract, skin, or mucous membranes.
571
ABOUT
Topical ointment/cream: 100,000 units/g in 15- and 30-g tubes. Ointment dissolved in
polyethylene and mineral-oil-gel base.
Topical powder: 100,000 units/g in 15- and 30-g plastic squeeze bottles.
Oral suspension: 100,000 units/mL in 60- and 473-mL bottles. Shake well before use and
do not freeze. Contains less than 1% alcohol and less than 50% sucrose [1].
572
Octreotide
Dose
Hyperinsulinemic hypoglycemia:
Initial dose: 1 mcg/kg/dose every 6 hours subQ or IV. Titrate upward to desired effect.
Initial response should occur within 8 hours; tachyphylaxis may occur within several days.
Maximum dose: 10 mcg/kg/dose every 6 hours.
Chylothorax:
Begin at 1 mcg/kg/hour IV continuous infusion. Titrate upward as necessary based on
reduction in chyle production; dosage increases of 1 mcg/kg/hour every 24 hours have been
used. Infusion is decreased gradually over 2 to 7 days.
Maximum dose: 10 mcg/kg/hour.
Has also been used subQ or IV in divided doses.
Uses
Refractory hyperinsulinemic hypoglycemia:.
Congenital and postoperative chylothorax, Adjunct:.
Administration
Subcutaneous: To minimize pain, use smallest volume to deliver dose. Rotate sites [1].
Intravenous: May give IV push over 3 minutes (or rapid IV bolus in emergency situations)
or by intermittent IV infusion over 15 to 30 minutes in compatible solution at a concentration
of 10 to 25 mcg/mL [1][2]. May also give by continuous IV infusion. Dilutions as low as 1
mcg/mL can be used.
MEDICATION SAFETY
Adverse Effects
Vomiting, diarrhea, abdominal distention and steatorrhea may occur. Pulmonary hypertension
has been reported in treated former premature infants with chronic lung disease. Necrotizing
enterocolitis has been reported in term neonates receiving octreotide for the treatment of
hyperinsulinemic hypoglycemia (6 cases) and chylothorax (2 cases). Hyperglycemia may
occur in patients being treated for chylothorax.
573
D5W and NS.
Heparin.
Micafungin.
Monitoring
Monitor blood glucose closely. Monitor for signs and symptoms of necrotizing enterocolitis.
Pharmacology
Octreotide is a long-acting analog of the natural hormone somatostatin. It is an even more

potent inhibitor of growth hormone, glucagon, and insulin than somatostatin. Like
somatostatin, it also suppresses LH response to GnRH, decreases splanchnic blood flow, and
inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and
pancreatic polypeptide. After subcutaneous injection, octreotide is absorbed rapidly and
completely from the injection site. The elimination half-life of octreotide from plasma is
approximately 1.7 hours in adults compared with 1 to 3 minutes for the natural hormone.
Excreted unchanged into the urine.
ABOUT
Availability: 1-mL single-dose ampules for injection containing 50-, 100-, or 500-mcg, and
in 5-mL multiple-dose vials in concentrations of 200 and 1000 mcg/mL. pH 3.9 to 4.5.
Osmolarity is 279 mOsm/kg.
574
Storage: Refrigerate and protect from light. Do not warm artificially. After initial use,
multiple dose vials should be discarded within 14 days. Ampuls should be opened just prior
to administration and the unused portion discarded.
For subQ injection, use undiluted drug unless dose volume is not accurately measurable. For
continuous IV administration, consider making a dilution of 10 to 25 mcg/mL using D5W or
NS.
575
Omeprazole
Dose
0.5 to 1.5 mg/kg/dose orally once daily.
Uses
MEDICATION SAFETY
CONTRAINDICATIONS
Concomitant use with rilpivirine-containing agents is contraindicated[4][5].
PRECAUTIONS
Acute interstitial nephritis may occur (typically due to idiopathic hypersensitivity
reaction); discontinue if it occurs [6].
Cyanocobalamin (vitamin B12) deficiency may occur with long term use [6].
576
infections)
Avoid concomitant use of clopidogrel, rifampin, and St. John's wort [8].
penetration; demonstrated in a retrospective cohort (n=293 children 2 years or younger) [9].
Adverse Effects
Hypergastrinemia and mild transaminase elevations are the only adverse effects reported in
children who received omeprazole for extended periods of time. Available data are limited to
small studies of infants and children.

, the use of PPI
Monitoring
Observe for symptomatic improvement within 3 days. Consider intraesophageal pH

monitoring to assess for efficacy (pH greater than 4.0). Measure AST and ALT if duration of
therapy is greater than 8 weeks. Hypomagnesemia has been reported with prolonged
hypomagnesemia.
Pharmacology
Omeprazole inhibits gastric acid secretion by inhibition of hydrogen-potassium ATPase, the

enzyme responsible for the final step in the secretion of hydrochloric acid by the gastric
parietal cell ("proton pump"). Onset of action is within one hour of administration, maximal
effect is at approximately 2 hours. Inhibition of acid secretion is about 50% of maximum at
24 hours and the duration of action is approximately 72 hours.
ABOUT
577
Zegerid® (omeprazole/sodium bicarbonate) is supplied as a 20-mg powder for suspension
packet. A 2-mg/mL concentration can be prepared by reconstituting up to a total volume of
10 mL with water. The appropriate dose can be administered through a nasogastric or
orogastric tube. The suspension should be flushed through the tube with water or normal
saline. Studies regarding stability of this product for partial doses have been conducted. A
suspension made from six 20-mg packets mixed to a final volume of 60 mL (final
concentration, 2 mg/mL) was stable under refrigeration for at least 45 days. In another
study, suspensions of 0.6 to 4 mg/mL were stable under refrigeration for up to 28 days;
suspensions of 1 to 4 mg/mL were stable at room temperature for 7 days, with a yellow color
change.
Prilosec® is supplied as 2.5-mg and 10-mg unit dose packets for delayed-release oral
suspension (omeprazole magnesium) and as delayed-release capsules containing 10, 20, or
40-mg omeprazole as enteric-coated granules.
To prepare the delayed-release suspension, empty the 2.5 mg packet into a container
containing 5 mL of water (or the 10 mg packet into a container containing 15 mL of water).
Stir and leave 2 to 3 minutes to thicken. Stir and administer appropriate patient-specific dose
within 30 minutes. For nasogastric or gastric tube administration, add 5 mL of water to a
catheter-tipped syringe then add contents of 2.5 mg packet (or add 15 mL of water to
syringe for adding 10 mg packet). Shake syringe immediately and leave 2 to 3 minutes to
thicken. Shake syringe and inject patient-specific dose through the tube within 30 minutes.
Flush tube with an appropriate amount of water.
Extemporaneous Suspensions: Studies regarding stability of this product for partial doses
have been conducted. A suspension made from six 20-mg packets mixed to a final volume of
60 mL (final concentration, 2 mg/mL) was stable under refrigeration for at least 45 days
[11]. In another study, suspensions of 0.6 to 4 mg/mL were stable under refrigeration for
up to 28 days; suspensions of 1 to 4 mg/mL were stable at room temperature for 7 days,
with a yellow color change [12].
578
Oseltamivir
Dose
Influenza, Treatment
Initiate within 48 hours of influenza symptom onset[1]. Some benefits may be apparent
when initiated after 48 hours of symptom onset in patients with severe, complicated or
progressive illness and in hospitalized patients [2].
Postmenstrual age less than 38 weeks: 1 mg/kg/dose orally twice daily for 5 days.
Longer treatment may be necessary for patients whose illness is prolonged, critically ill
patients with respiratory failure, or immunosuppressed people [2] .
Postmenstrual age 38 to 40 weeks: 1.5 mg/kg/dose orally twice daily for 5 days. Longer
treatment may be necessary for patients whose illness is prolonged, critically ill patients with
respiratory failure, or immunosuppressed people [2] .
Postmenstrual age greater than 40 weeks: 3 mg/kg/dose orally twice daily for 5 days.
Longer treatment may be necessary for patients whose illness is prolonged, critically ill
patients with respiratory failure, or immunosuppressed people [2].
2 weeks to younger than 1 year: 3 mg/kg/dose orally twice daily for 5 days [1]. Longer
treatment may be necessary for patients whose illness is prolonged, critically ill patients with
respiratory failure, or immunosuppressed people [2].
Uses
Treatment of confirmed or suspected influenza virus for patients who have severe,
complicated, or progressive illness, patients at higher risk of influenza complications (eg, age
or underlying medical condition) or who are hospitalized. Early antiviral treatment can
shorten the duration of fever and clinical illness, may reduce the risk of complications (eg,
otitis media, pneumonia, respiratory) and death, and shorten the duration of hospitalization
[4][5]. Those patients with severe, complicated or progressive illness and those who are
hospitalized may also derive benefit even if oseltamivir is started after 48 hours of illness
onset [4].
Treatment should not wait for laboratory confirmation of influenza, but instead be initiated as
soon as possible after the onset of symptoms, including patients seeking medical attention
more than 48 hours after onset of symptoms. The duration of therapy is 5 days [4][5], but a
longer treatment duration may be considered in patients who remain severely ill after 5 days
of treatment. Unless an alternative diagnosis is made, a full treatment course should be
completed by patients with suspected influenza regardless of negative initial test results [4].
Oseltamivir has been used in term and preterm infants in the NICU setting for treatment and
prophylaxis of influenza A virus (H1N1) with no reported safety concerns [6][7].
Neuraminidase inhibitors reduced the mortality rate (odds ratio, 0.36 (95% CI, 0.16 to 0.84),
particularly if mechanical ventilation was required, in children (median age 6 years (0 to 17
years)) in the intensive care unit with laboratory-confirmed influenza in a retrospective study
(n=784). Early treatment (3 days vs 5 days) was associated with decreased mortality [8].
579
Administration
May be given with or without food. Food may increase tolerability in some patients [3].
MEDICATION SAFETY
Precautions
Concomitant use: Concomitant use with intranasal live attenuated influenza vaccine (LAIV)
not recommended within 2 weeks before or 48 hours after oseltamivir phosphate
administration unless medically necessary [9]
Dermatologic: Serious skin reactions such as toxic epidermal necrolysis, Stevens-Johnson
Syndrome, and erythema multiforme may occur; discontinue use if allergic-like reaction
occurs [9]
Fructose intolerance: One dose delivers 2 g of sorbitol and may cause dyspepsia or
diarrhea in patients with hereditary fructose intolerance [9].
Immunologic: Anaphylaxis has been reported; discontinue use if allergic-like reaction
occurs [9]
Immunologic: Secondary bacterial infections may occur [9]
Psychiatric: Abnormal behavior and delirium leading to potentially fatal injuries have been
reported, primarily in pediatric patients [9]
Renal: Renal impairment (ESRD not undergoing dialysis); use not recommended [9]
Adverse Effects
Most common adverse events reported in pediatric patients are nausea and vomiting [3].
Mild rash and gastrointestinal signs, and transient rise in transaminases have been reported
in neonates receiving oseltamivir; no abnormal neurologic manifestations were reported.
Monitoring
Closely monitor patients with influenza for neurologic symptoms or abnormal behavior [9].
Pharmacology
Oseltamivir phosphate, through its active form oseltamivir carboxylate, inhibits influenza virus
neuraminidase which affects viral particle release. Oseltamivir exhibits activity against
influenza A and influenza B viruses. Bioavailability is approximately 75%. Food has no effect
580
on absorption. Minimal protein binding (3% for oseltamivir carboxylate). Extensively
metabolized in the liver to oseltamivir carboxylate by esterases. Primarily eliminated in the
kidneys (greater than 90%). Clearance is faster in younger pediatric patients compared with
adults. Elimination half-life ranges from 1 to 3 hours [3]. There are very limited
pharmacokinetic data in neonates or preterm infants, but it appears preterm infants would
require a lower dose than term infants [10][11].
ABOUT
Available as 30-mg, 45-mg, and 75-mg capsules and oral suspension (6 mg/mL when
reconstituted) [3].
Oral Suspension
In July 2011, the manufacturer changed the commercially available suspension concentration
from 12 mg/mL to 6 mg/mL. There were no quality issues with the 12 mg/mL product;
therefore, the 12 mg/mL suspension may remain in the marketplace and in state or national
stockpiles until such supplies expire. The 12 mg/mL concentration will no longer be marketed
after current supplies run out [12].
To reconstitute oral suspension, add 55 mL of water to bottle and shake well for 15 seconds.
The oral suspension has a concentration of 6 mg/mL after reconstitution. Stable for 17 days
refrigerated or 10 days if stored at room temperature [3].
Oseltamivir oral suspension contains 2 g of sorbitol per 75 mg dose, which exceeds the
maximum daily sorbitol limit in patients with hereditary fructose intolerance, and may cause
dyspepsia and diarrhea in these patients [3].
Emergency Compounding
During shortage of commercially manufactured oseltamivir (Tamiflu®) oral suspension, the
suspension can be compounded using oseltamivir 75 mg capsules. The compounded
suspension yields a 6 mg/mL concentration (same as commercially available 6 mg/mL
suspension) and total volume adequate for 1 patient for a 5-day course of treatment or a 10-
day course of prophylaxis. The compounded suspension is only to be used in emergency
situations, and should not be used for convenience or when the commercially manufactured
suspension is available [3].
Directions for Compounding
Determine dose and total volume required for compounding. For a dose of 15 mg or
less, total volume is 37.5 mL; for 30 mg, total volume is 75 mL; for 45 mg, total volume
is 100 mL; for 60 mg, total volume is 125 mL; for 75 mg, total volume is 150 mL. If the
dose is between these doses, default to the next greater dose and volume.
Determine number of capsules, volume of water, and volume of vehicle required. Place
specified amount of water into a polyethyleneterephthalate (PET) or glass bottle (2.5
mL for 3 capsules; 5 mL for 6 capsules; 7 mL for 8 capsules; 8 mL for 10 capsules; 10
mL for 12 capsules).
Transfer contents of required number of oseltamivir 75 mg capsules into the PET or
glass bottle and gently swirl for at least 2 minutes; slowly add the specified volume of
vehicle (cherry syrup, Ora-Sweet(R) sugar-free, or simple syrup: 34.5 mL for 3 capsules
(total volume, 37.5 mL); 69 mL for 6 capsules (total volume, 75 mL); 91 mL for 8
capsules (total volume, 100 mL); 115 mL for 10 capsules (total volume, 125 mL); 137
mL for 12 capsules (total volume, 150 mL).
581
Close the bottle and shake well for 30 seconds to dissolve active drug; stable for 35
days when refrigerated (2 to 8 degrees C) or for 5 days at room temperature.
582
Oxacillin
Dose
Usual dosage: 25 mg/kg/dose IV over at least 10 minutes.

Meningitis: 50 mg/kg/dose IV over at least 10 minutes.


0 to 28 12
≤29
>28 8
0 to 14 12
30 to 36
>14 8
0 to 7 12
37 to 44
>7 8
≥45 ALL 6
Uses
Penicillinase-producing staphylococci infections.

https://doi.org/10.1161/CIR.0000000000000298

Streptococci
https://www.micromedexsolutions.com/micromedex2/librarian/CS/9D8FCE/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
583
CefTRIAXone +
gentamicin (not for
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)
Baltimore, 2015
Administration
Intravenous: Administer IV push over 10 minutes at a concentration not exceeding

100 mg/mL. For intermittent IV infusion, dilute to a concentration of 10 to 40 mg/mL and
infuse over 15 to 60 minutes.
MEDICATION SAFETY
584
Adverse Effects
Interstitial nephritis associated with hematuria, albuminuria, and casts in urine. Bone marrow
depression. Elevated AST and ALT. Hypersensitivity in the form of a rash. Tolerant strains of
staphylococci have been reported.
D5W, D10W, and NS.
Acyclovir, cefotaxime, cefoxitin, chloramphenicol, dopamine, famotidine, fluconazole, heparin,

hydrocortisone succinate, magnesium sulfate, milrinone, morphine, potassium chloride, and
zidovudine.
Amikacin, caffeine citrate, gentamicin, netilmicin, sodium bicarbonate, and tobramycin.
Monitoring
Periodic CBC and urinalysis. AST, ALT. Irritating to veins--watch for phlebitis.
Observe IV site for signs of extravasation.
Pharmacology
Inhibits synthesis of bacterial cell wall. Rapidly excreted renally unchanged. Poor CSF
penetration. Good penetration of pleural, pericardial, and synovial fluids.
ABOUT
585
Available as powder injection in 250-mg, 500-mg, 1-g, 2-g, and 10-g vials. Reconstitute 250
mg vial with 5 mL of sterile water for injection to make a concentration of 50 mg/mL.
Reconstituted solution is stable for 4 days at room temperature, 7 days refrigerated. Dilute
further using sterile water or NS to a concentration less than or equal to 40 mg/mL. Dilution
stable for 4 days refrigerated.
586
Palivizumab
Dose
15 mg/kg per dose IM, preferably in the anterolateral aspect of the thigh [1]. Once the
patient qualifies for initiation of prophylaxis, it should continue throughout the respiratory
syncytial virus (RSV) season; maximum 5 monthly doses. Less than 5 doses is needed if
born during RSV season. Discontinue if breakthrough RSV hospitalization occurs. Consider a
postsurgical dose after procedures that include cardiopulmonary bypass or at the end of
extracorporeal membrane oxygenation in infants younger than 24 months who are receiving
prophylaxis and will continue to require prophylaxis [2][3].
Neonates who qualified for RSV prophylaxis may be given first dose 48 to 72 hours before
hospital discharge or promptly after discharge. For most areas of the US, if prophylaxis is
initiated in October, the fifth and final dose should be in February; if initiated in December,
fifth and final dose should be in April. Various regions of Alaska and Florida may have
different onset and end of the RSV season; RSV surveillance data generated by these States
may assist with the timing of the first dose [2][3].
Uses
AAP Recommendations: For prophylaxis during RSV season restricted to the populations
detailed below [2][3].
Preterm infants without chronic lung disease (CLD) of prematurity or congenital
heart disease (CHD): May administer palivizumab in the first year of life if born before 29
weeks, 0 days gestation who are younger than 12 months at start of RSV season. NOT
universally recommended if born at 29 weeks, 0 days gestation or later [2][3]. Palivizumab
was associated with a significantly reduced rate of hospitalization for RSV (3.1% vs 5%), but
the rate of hospitalization for bronchiolitis without RSV diagnosis was increased (3.3% vs
1.9%, p=0.05) in infants 29 to 32 weeks' gestation. No difference was observed for those
infants 33 to 36 weeks' gestation in a retrospective study (N=14,097) [4].
Preterm infants with CLD of prematurity: May be considered in first year of life during
RSV season in preterm infants who develop CLD of prematurity (ie, gestational age younger
than 32 weeks, 0 days and require more than 21% oxygen for at least the first 28 days after
birth). May be considered in the second year of life ONLY in patients with CLD of prematurity
who still require medical therapy, such as chronic corticosteroids, diuretics, or supplemental
oxygen, during the 6-month period before the second RSV season begins [2][3].
Infants with hemodynamically significant heart disease: May be considered in the first
year of life for infants with conditions such as acyanotic heart disease requiring medications
for heart failure and anticipatory cardiac surgery as well as moderate to severe pulmonary
hypertension. May also consider in children younger than 24 months who undergo cardiac
transplantation during RSV season [2][3].
Children with anatomic pulmonary abnormalities or neuromuscular disease: Consider
prophylaxis during first year of life if condition impairs clearance of secretions from upper
airway [2][3].
Alaskan native populations: Due to cost associated with transportation from remote areas
and burden of disease, prophylaxis may be justified [2][3].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/26A93D/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
587
Navajo and White Mountain Apache infants: Data are insufficient but prophylaxis may
be justified [2][3].
Profoundly immunocompromised and younger than 24 months: Consider prophylaxis
during RSV season [2][3].
Children with Down syndrome: Data are insufficient to establish efficacy for RSV
infection prophylaxis [2][3].
Children with cystic fibrosis (CF): A single randomized controlled trial (n=186 infants;
age range 0.4 to 24.4 months) did not detect any clinically meaningful differences between 5
monthly injections of palivizumab and placebo after 12 months of follow-up [5]. There was
some evidence in non-randomized studies to support a role for prophylactic palivizumab in
reduction of hospitalizations due to respiratory syncytial virus in a systematic review of 10
studies in 3,891 children 2 years or younger with CF; however, there was substantial inter-
study variation in regimens used, risk of bias was moderate to serious, and safety and
tolerability could not be ascertained [6]. Prophylaxis in children with CF is not recommended
unless the child qualifies for other reasons. Consider prophylaxis if chronic lung disease is
clinically evident and/or nutritional compromise is present in the first year of life.
Manifestation of severe lung disease or weight less than 10th percentile may justify use
through the second year [2][3].
Not Recommended: Infants and children with hemodynamically insignificant heart disease
(eg, secundum atrial septal defect, small ventricular septal defect, pulmonic stenosis,
uncomplicated aortic stenosis, mild coarctation of the aorta, and patent ductus arteriosus).
Infants with lesions sufficiently revised with surgery, unless continued medication for
congestive heart failure is required. Infants with mild cardiomyopathy who do not receive
medical treatment for cardiomyopathy. Children in the second year of life who do not rely on
medical support. For the prevention of healthcare-associated RSV disease [2][3].
Alternative regimen (based on mathematical modeling): Administer the second dose

29 days after the first and then subsequent doses every 38 days (total of 4 or 5 doses);
initiate palivizumab on a fixed start date based on longitudinal local RSV data from previous
seasons. This alternative regimen provides protection for regions that experience early
and/or prolonged RSV seasons [7].
Palivizumab treatment in high-risk infants reduced the risk of RSV hospitalizations (relative
risk (RR), 0.49 (95% CI, 0.37 to 0.64)) and the frequency of intensive care admissions (RR,
0.5 (95% CI, 0.3 to 0.81) by half compared with placebo in a meta-analysis (3 studies,
n=2831). Economic evaluations from review of 34 additional studies ranged from highly cost-
effective to not cost-effective; all studies were sponsored by pharmaceutical companies [8].

Indicated for the prevention of serious lower respiratory tract disease due to respiratory
syncytial virus (RSV) in pediatric patients with: [9]
a history of premature birth (≤35 weeks gestational age) and who are 6 months of age
or younger at the start of RSV season
bronchopulmonary dysplasia that required medical treatment within the last 6 months
and who are 24 months of age or younger at the start of RSV season
hemodynamically significant congenital heart disease and who are 24 months of age or
younger at the start of RSV season
Limitations of use: Not indicated for the treatment of RSV disease [9].
MEDICATION SAFETY
588
Precautions
Anaphylaxis, anaphylactic shock, and other acute hypersensitivity reactions, some severe
and/or fatal, have been reported on initial exposure or re-exposure to palivizumab;
permanently discontinue if a severe hypersensitivity reaction occurs. Do not administer to
patients who have had a previous significant hypersensitivity reaction to palivizumab [1].
Adverse Effects
In clinical trials, fever and rash occurred slightly more frequently in palivizumab recipients
(27% and 12%, respectively) compared with those who received placebo (25% and 10%,
respectively) [1].
Monitoring
Observe injection site for induration and swelling.
Pharmacology
Synagis ® is a humanized monoclonal antibody produced by recombinant DNA technology.

This composite of human (95%) and murine (5%) antibody sequences inhibits RSV
replication. The mean half-life of Synagis ® is approximately 20 days. Adequate antibody
titers are maintained in most infants for one month following a 15-mg/kg dose. Due to a
faster metabolic rate, some hospitalized very low birth weight infants (less than 500 g) may
not maintain optimal RSV titers for the entire initial month until after the second dose.
Palivizumab does not interfere with the response to other vaccines and as such, they can be
administered concurrently.
ABOUT
Synagis® is supplied as 50-mg and 100-mg single-dose vials in ready-to-use, NO

RECONSTITUTION required, liquid solution. Do not add any diluent to the liquid solution
and use one dose per vial. Do not re-enter vial after initial withdrawal and discard any
unused portions. Administer as soon as possible after withdrawal from the vial. Do not
FREEZE or SHAKE.
The liquid solution should be stored refrigerated between 2 to 8 degrees C (36 to 46

589
degrees F). Synagis® contains no preservatives, thimerosal, or other mercury salts. Rubber
stopper on top of vials does not contain latex [1].
590
Pancuronium
Dose
Skeletal Muscle Relaxation/Paralysis:

Test dose: 0.02 mg/kg IV to measure responsiveness [1].
0.1 mg/kg (0.04 to 0.15 mg/kg) IV push, as needed for paralysis. Usual dosing interval is 1
to 2 hours. Adjust dose as needed based on duration of paralysis.
Uses
Skeletal muscle relaxation/paralysis in infants requiring mechanical ventilation. Proposed

desirable effects are improved oxygenation/ ventilation, reduced barotrauma, and reduced
fluctuations in cerebral blood flow.
Administration
Must be accompanied by adequate analgesia and/or sedation[1].

Administer IV push over 5 to 10 seconds. Has also been administered by continuous infusion.
Concentrations are 1 to 2 mg/mL [2]. May also be diluted to 0.5 mg/mL.
MEDICATION SAFETY
Adverse Effects
Hypoxemia may occur because of inadequate mechanical ventilation and deterioration in

pulmonary mechanics. Tachycardia and blood pressure changes (both hypotension and
hypertension) occur frequently. Increased salivation.
Black Box Warning
According to the manufacturer's black box warning, pancuronium should be administered by

adequately trained individuals familiar with its actions, characteristics, and hazards.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/81250C/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
591
D5W, NS, and Lactated Ringer's.
Aminophylline, caffeine citrate, cefazolin, cimetidine, dobutamine, dopamine, epinephrine,

esmolol, fentanyl, fluconazole, gentamicin, heparin, hydrocortisone succinate, isoproterenol,
lorazepam, midazolam, milrinone, morphine, nitroglycerin, nitroprusside, propofol, ranitidine,
trimethoprim-sulfamethoxazole, and vancomycin.
Pentobarbital and phenobarbital.
Monitoring
Monitor vital signs frequently, blood pressure continuously. Use some form of eye lubrication.
Pharmacology
Nondepolarizing muscle-relaxant that competitively antagonizes autonomic cholinergic

receptors and also causes sympathetic stimulation. Partially hydroxylated by the liver, 40%
excreted unchanged in urine. Onset of action is 1 to 2 minutes; duration varies with dose and
age. Reversed by neostigmine and atropine.
Factors affecting duration of neuromuscular blockade:
Potentiation: Acidosis, hypothermia, neuromuscular disease, hepatic disease, renal failure,
cardiovascular disease, younger age, aminoglycosides, hypermagnesemia, and hypokalemia.
Antagonism: Alkalosis, epinephrine, and hyperkalemia.
Sensation remains intact; analgesia should be used for painful procedures.
ABOUT
Available in concentrations of 1 mg/mL (10-mL vials) and 2 mg/mL (2-mL and 5-mL vials).
Products contain 1% (10 mg/mL) benzyl alcohol. Product maintains full clinical potency for 6
months if kept at room temperature or 36 months when refrigerated. Stable for 48 hours
592
when further diluted in compatible solution.
593
Pantoprazole
Dose
2.5 mg orally every day in preterm and term neonates provided similar or slightly higher
exposure compared with 40 mg orally in adults or older children in pharmacokinetic studies
[1][2]. Gastric pH and the percentage of time with gastric pH above 4 were achieved, but no
effect on esophageal pH, in 45 term and preterm neonates receiving 2.5 mg orally every day
[3][4].
Uses
Gastroesophageal reflux disease (GERD): Proton pump inhibitors (PPIs) are the first-
A systematic review of 5 placebo-controlled studies demonstrated a lack of effectiveness of
proton pump inhibitors (lansoprazole, omeprazole, and pantoprazole) in reducing GERD
symptoms in infants (34 weeks' postmenstrual age to 12 months) [10]. Pantoprazole did not
improve symptoms in 129 pediatric patients 1 through 11 months of age with symptomatic
GERD in a multicenter, randomized, double-blind, placebo-controlled study [3].
Stress ulcer prophylaxis: Despite the lack of data, prophylaxis with a proton pump
inhibitor or H2RA is frequently used in pediatric [11][12] and neonatal intensive care units
[11]. Prophylaxis in critically ill children admitted to the intensive care unit may be beneficial
based on a systematic review of 2 studies; however the evidence was of low quality. The
treatments were almagate, ranitidine, sucralfate, and omeprazole [13]. In prepubertal
594
children with severe sepsis, experts provide no recommendation on the use of stress ulcer
prophylaxis [14]. Based on low to very low quality evidence in patients older than 16 years
some experts suggest acid suppression (PPIs or H2RA) in the intensive care setting for
acutely ill patients for the primary prevention of upper gastrointestinal bleeding [15].
In adults, prophylaxis (proton pump inhibitor or H2RA) is recommended in patients with
sepsis or septic shock who have risk factors for gastrointestinal bleeding. Prophylaxis should
only be used in patients with risk factors [16][17].
Upper Gastrointestinal (UGI) bleeding: Acid suppression is recommended in pediatric

UGI bleeds, which is supported by adult data using proton-pump inhibitors [18].

Not FDA approved in neonate patients [3][5].
Administration
Oral
Delayed-Release Suspension: Mix the pantoprazole with 2.5 mL of water and
immediately administer with an oral syringe. Administer 30 minutes before the first feeding
at approximately the same time each day [2].
Nasogastric or Gastric Tube

Delayed-Release Suspension: Remove the plunger from the barrel of a 60-mL catheter-
tip syringe. Connect the catheter tip of the syringe to a 16 French (or larger) tube. Hold the
syringe attached to the tubing as high as possible while giving to prevent any bending of the
tubing. Empty the contents of the packet into the barrel of the syringe and add 10 mL of
apple juice; gently tap and/or shake the barrel of the syringe to help rinse the syringe and
tube. Repeat at least twice more using the same amount of apple juice (10 mL) each time.
No granules should remain in the syringe [3].
Intravenous: Administer as an IV infusion over 15 to 30 minutes at a concentration of 0.4

to 0.8 mg/mL [5][6] or IV push over 2 minutes at a concentration of 4 mg/mL. Flush IV line
before and after administration with NS, D5W, or LR [5].
MEDICATION SAFETY
CONTRAINDICATIONS
Contraindicated [3][5]
Known hypersensitivity to any component or any substituted benzimidazole
Concomitant use of rilpivirine-containing products
PRECAUTIONS
Concomitant use: Elevation or and prolongation of methotrexate concentrations and/or its
metabolite may occur; temporary withdrawal of proton pump inhibitor may be necessary [5].
595
Cardiovascular: Thrombophlebitis was associated with IV administration [5].
Endocrine and metabolic: Zinc supplementation may be needed in patients who are prone
to zinc deficiency and receiving IV pantoprazole, which contains a chelator (edetate disodium
(EDTA)). Use caution when other EDTA-containing products are co-administered IV [5].
Endocrine and metabolic: Hypomagnesemia has been reported in patients treated with
proton pump inhibitors for at least 3 months; tetany, arrhythmias, and seizures may occur;
discontinuation may be required [3].
Endocrine and metabolic: Vitamin B12 deficiency may occur with prolonged use (e.g.,
longer than 3 years) [3].
Gastrointestinal: Symptomatic response does not preclude presence of gastric malignancy
[3].
Gastrointestinal: Clostridium difficile-associated diarrhea may occur, especially in
hospitalized patients; use lowest dose and shortest treatment duration [3].
Hepatic: Mild, transient transaminase elevations have been observed with pantoprazole;
clinical significant is unknown [5].
Immunologic: Anaphylaxis and other serious reactions such as erythema multiforme,
Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported with IV
pantoprazole [3]
Immunologic: New or worsening systemic or cutaneous lupus erythematosus has been
reported within weeks to years of treatment initiation; avoid using for longer than medically
indicated and discontinue use if suspected [3].
Infections: Increased risk of infections (necrotizing enterocolitis, pneumonia, upper
infections)
Lab interference: Gastric acid suppression may increase serum chromogranin A (CgA)
levels; withhold pantoprazole for at least 14 days prior to neuroendocrine tumor assessment
based on CgA levels [21]
Musculoskeletal: Osteoporosis-related bone fracture of hip, wrist, or spine may occur,
especially with higher (multiple daily) doses or longer duration of therapy (1 year or longer);
use lowest dose and shortest treatment duration [3].
Renal: Acute interstitial nephritis, typically associated with idiopathic hypersensitivity, has
been reported; discontinuation required [3].
penetration; demonstrated in a retrospective cohort (n=293 children 2 years or younger)
[22].
Adverse Effects
Reported adverse effects in neonates: [4][2]

Anemia
Constipation
Contact dermatitis
Hypoxia
Vomiting
Rhinitis
Anemia (n=6), constipation (n=5), vomiting (n=3), hypoxia (n=5), rhinitis (n=2), and
contact dermatitis (n=2) occurred in term and preterm neonates (n=61) administered
596
pantoprazole [4][2]. One patient experienced excessive vomiting, which was probably related
to pantoprazole [4].
Adverse effects reported in more than 4% of pediatric patients (1 to 16 years of age) were
headache, fever, abdominal pain, vomiting, diarrhea, upper respiratory infection, and rash
[3].

, the use of PPI
NS, D5W, and LR.
Pantoprazole diluted to concentration of 0.8 mg/mL:

Ampicillin (10 to 40 mg/mL), cefazolin (20 to 40 mg/mL), ceftriaxone (20 to 40 mg/mL),
dopamine (0.8 to 3.2 mg/mL), epinephrine (16 to 32 mcg/mL), furosemide (1 to 2 mg/mL),
insulin (5 to 50 units/mL), morphine (1 to 10 mg/mL), potassium chloride (20 mEq/L).
Pantoprazole diluted to concentration of 0.4 mg/mL:

Acyclovir (7 mg/mL), amikacin (5 mg/mL), aminophylline (2.5 mg/mL), amphotericin B lipid
complex (1 mg/mL), amphotericin B liposome (1 mg/mL), ampicillin (10 to 40 mg/mL),
ampicillin/sulbactam (20 mg/mL ampicillin), argatroban (1 mg/mL), azithromycin (2 mg/mL),
bumetanide (40 mcg/mL), calcium gluconate (40 mg/mL), cefazolin (20 to 40 mg/mL),
cefoxitin (20 mg/mL), ceftazidime (40 mg/mL), ceftriaxone (20 to 40 mg/mL), cefuroxime
(30 mg/mL), clindamycin (10 mg/mL), digoxin (0.25 mg/mL), dopamine (0.8 to 3.2 mg/mL),
enalaprilat (0.1 mg/mL), epinephrine (16 to 32 mcg/mL and 50 mcg/mL), ertapenem (20
mg/mL), fosphenytoin (20 mg PE/mL), furosemide (1 to 2 mg/mL and 3 mg/mL), ganciclovir
(20 mg/mL), gentamicin (5 mg/mL), granisetron (50 mcg/mL), heparin (100 units/mL),
hydrocortisone (1 mg/mL), imipenem/cilastatin (5 mg/mL imipenem), insulin (1 unit/mL and
5 to 50 units/mL), magnesium sulfate (100 mg/mL), metoclopramide (5 mg/mL), morphine
(1 to 10 mg/mL), nafcillin (20 mg/mL), nitroprusside (2 mg/mL), pentobarbital (5 mg/mL),
phenobarbital (5 mg/mL), phentolamine (0.2 mg/mL), piperacillin/tazobactam (40 mg/mL
piperacillin), potassium chloride (20 mEq/L and 100 mEq/L), procainamide (20 mg/mL),
sodium bicarbonate (1 mEq/mL), trimethoprim/sulfamethoxazole (0.8 mg/mL trimethoprim),
ticarcillin/clavulanate (31 mg/mL ticarcillin), tobramycin (5 mg/mL), zidovudine (4 mg/mL).
Amphotericin B, aztreonam, calcium chloride, caspofungin, cefepime, cefotaxime, cefotetan,

chloramphenicol, cimetidine, ciprofloxacin, dexamethasone, diazepam, dobutamine,
dolasetron, esmolol, famotidine, fentanyl, fluconazole, hydralazine, lidocaine, linezolid,
597
lorazepam, methylprednisolone, metronidazole, midazolam, milrinone, naloxone, nicardipine,
ondansetron, pancuronium, phenytoin, propranolol, quinupristin/dalfopristin, ranitidine,
rocuronium, vancomycin, vecuronium.
Monitoring
Laboratory Findings
pH: Consider intraesophageal pH monitoring to assess for efficacy (pH greater than 4) [19].
Magnesium Concentration: Hypomagnesemia has been reported with prolonged
hypomagnesemia [3].
Pharmacology
Mechanism of action: Pantoprazole inhibits gastric acid secretion by inhibition of

hydrogen-potassium ATPase, the enzyme responsible for the final step in the secretion of
hydrochloric acid by the gastric parietal cell ("proton pump"). Antisecretory activity persists
for greater than 24 hours [5].
Bioavailability: 77% [3].

AUC: 3.54 mcg X hr/mL for 1.25 mg single-oral-dose in 14 infants and 7.27 mcg X hr/mL for
2.5 mg single-oral dose in 19 infants. Infants had a corrected postmenstrual age of less than
44 weeks and a weight of 1500 g or more [2].
Protein-binding: Approximately 98% (mainly to albumin) [3].
Metabolism: Extensively metabolized in the liver by CYP2C19 and to a minor extent CYP3A4
isoenzymes [3]. Polymorphism may be displayed with the CYP2C19 isoenzyme, leading to
poor metabolizers of the drug. In a pediatric (5 to 16 years of age) pharmacokinetic study,
poor metabolizers (n=3) had a 6- to 14-fold increase in AUC and a 10-fold increase in half-
life compared to extensive metabolizers (n=21) [24].
Excretion
Eliminated in the urine (71%) and feces (18%) [3].
Clearance: 0.21 to 0.23 L/hr/kg in 33 infants (corrected postmenstrual age of less than 44
weeks and a weight of 1500 g or more) administered a single-oral-dose of 1.25 or 2.5 mg
oral pantoprazole [2]. Apparent oral clearance (L/hr/kg) was highest in the 1 to 6 years age
range (1.28 to 2.08 L/hr/kg), with lower values in infants 1 to 12 months (0.87 to 1.54
L/hr/kg) [25], and children 6 years and older (0.18 to 0.41 L/hr/kg) [26].
Half-life: The mean half-lives were 3.1 hours for a 1.25 mg and 2.7 hours for the 2.5 mg
oral dose in 40 infants (gestational age, 23 to 41 weeks and postnatal age, 1.3 to 19.6
weeks) [2]. Mean half-lives were approximately 1.42 to 5.34 hours and 0.7 to 0.9 hours in
pediatric patients aged 1 month to 6 years [25] and 6 to 16 years, respectively [26].
598
ABOUT
Oral Route
Availability: 40-mg packets containing granules for delayed-release suspension and 20-mg
and 40-mg delayed-release tablets [3].
Storage: Store at a controlled room temperature between 20 and 25 degrees C (68 and 77
degrees F), with excursions permitted between 15 and 30 degrees C (59 and 86 degrees F)
[3].
Preparation: Make an inert powder blend with pantoprazole 2.5 mg granules. May add
grape flavoring. Provided in a pouch for immediate administration after mixing with 2.5 mL of
water [1][2].
Extemporaneous Oral Suspension (2 mg/mL)

Suspension is stable for 62 days under refrigeration. Shake well before using [27].
Remove imprint from twenty 40-mg pantoprazole tablets and allow to dry
Triturate the tablets, transfer to a beaker and add 340 mL of sterile water for irrigation,
and place the beaker on a magnetic stirrer.
Add 16.8 g of sodium bicarbonate powder and stir for about 20 minutes until the tablet
remnants have disintegrated and the coating has dissolved.
While stirring, add another 16.8 g of sodium bicarbonate powder and stir for about five
minutes until the powder dissolves.
Add enough sterile water for irrigation to bring the final volume to 400 mL and mix well
Injection Route
Availability: 40-mg freeze-dried powder in single-use vials [5].
Reconstitution: Dilute vial with 10 mL of NS for a concentration of 4 mg/mL. May be given
IV push at this concentration. Reconstituted solution may be stored for up to 24 hours at
room temperature prior to IV infusion and does not need to be protected from light. Do not
freeze [5]
Dilution: Further dilute the reconstituted solution (4 mg/mL) with a compatible diluent to a
concentration of 0.4 or 0.8 mg/mL. Reconstituted solution is stable for 6 hours at room
temperature prior to further dilution. The admixture is stable for 24 hours from the time of
initial reconstitution at room temperature. Does not need to be protected from light. Do not
freeze [5].
599
Papaverine
Dose
30 mg per 250 mL of arterial catheter infusion solution [1][2].
Uses
Prolongation of peripheral arterial catheter patency [1][2].
Administration
Administer a 0.12 mg/mL papaverine solution in NS or ½ NS with heparin (1 unit/mL) via

intra-arterial catheter [1][2].
MEDICATION SAFETY
Adverse Effects
Use with caution in VLBW infants in the first days after birth due to potential of developing or
extending an intracranial hemorrhage. Chronic hepatitis, as evidenced by an increase in
serum bilirubin and serum glutamic transaminase, has been reported in three adults following
long-term papaverine therapy. One patient had jaundice, and another had abnormal liver
function on biopsy.
NS, 0.45 NS, both with 1 unit/mL heparin.
Lactated Ringer's (precipitate forms).
600
Phentolamine.
Pharmacology
Papaverine directly relaxes the tonus of various smooth muscle, especially when it has been
spasmodically contracted. It relaxes the smooth musculature of the larger blood vessels,
especially coronary, systemic peripheral and pulmonary arteries. Vasodilation may be related
to its ability to inhibit cyclic nucleotide phosphodiesterase, thus increasing levels of
intracellular cyclic AMP. During administration, the muscle cell is not paralyzed and still
responds to drugs and other stimuli causing contraction. Possibly because of its direct
vasodilating action on cerebral blood vessels, papaverine increases cerebral blood flow and
decreases cerebral vascular resistance in healthy subjects; oxygen consumption is unaltered.
Papaverine is metabolized in the liver and excreted in the urine in an inactive form.
ABOUT
Supplied as 30-mg/mL solution for injection in 2-mL preservative-free vials and 10-mL
multiple dose vials containing 0.5% chlorobutanol as a preservative. Vials also contain
edetate disodium 0.005%.
601
Penicillin G benzathine
Dose
Congenital Syphilis: 50,000 units/kg/dose IM as a single dose [1].
Uses
Treatment of congenital syphilis in infants during the first month of life. Recommended
as an alternative to aqueous crystalline penicillin G or procaine penicillin G in infants who
have a normal physical examination and a serum quantitative nontreponemal titer the same
or less than fourfold the maternal titer and the:
mother was not treated, inadequately treated, or has no documentation of having
received treatment;
mother was treated with erythromycin or another non-penicillin regimen; OR
mother received treatment less than 4 weeks before delivery.
Also recommended in infants whose mother was adequately treated during pregnancy (and
treatment given greater than 4 weeks before delivery) and mother has no evidence of
reinfection or relapse. Close serologic testing may be used instead of treatment in infants
whose mother's nontreponemal titers decreased fourfold after appropriate therapy for early
syphilis and remained stable or low for late syphilis.
For infants whose mother's treatment was adequate before pregnancy and nontreponemal
serologic titer remained low and stable before and during pregnancy and at delivery (VDRL
less than 1:2; RPR less than 1:4), no treatment is required; however, it may be considered if
follow-up is not assured.
Disease Recommended Treatment Alternative Treatment

Congenital Syphilis
Aqueous Crystalline Penicillin G or Procaine
(proven or highly N/A
Penicillin G
probable)
Congenital Syphilis Aqueous Crystalline Penicillin G, Procaine
N/A
(possible) Penicillin G, or Benzathine Penicillin G
Congenital Syphilis
Benzathine Penicillin G N/A
(less likely)
Consider benzathine
No treatment required. Serological follow up
Congenital Syphilis penicillin G if follow up is
recommended in infants with reactive
(unlikely) uncertain or a reactive test
nontreponemal tests.
occurs
Congenital Syphilis
Aqueous Crystalline Penicillin G N/A
(infants and children)
CDC Sexually Transmitted Diseases Treatment Guidelines, 2015
602
Administration
Inspect visually for particulate matter and discoloration prior to administration. For deep IM
injection only. Do not inject into or near an artery or nerve. Do NOT inject IV or
admix with other IV solutions since this has been associated with
cardiorespiratory arrest and death. Do not inject into the anterolateral thigh as
quadriceps femoris fibrosis and atrophy have been reported. Administer into the upper, outer
quadrant of the buttock (dorsogluteal) or the ventrogluteal site; in neonates, infants, and
small children, it may be preferable to administer into the midlateral aspect of the thigh.
When doses are repeated, vary the injection site. If any discoloration appears in the cartridge
upon insertion of the needle and aspiration, withdraw the needle and discard the glass
TUBEX(R) cartridge. To avoid blockage of the needle, administer at a slow steady rate [2].
MEDICATION SAFETY
Adverse Effects
Serious and potentially fatal hypersensitivity reactions have occurred. The Jarisch-Herxheimer
reaction (fever, chills, myalgia, headache, tachycardia, hyperventilation, mild hypotension)
may occur after initiation of therapy in patients with syphilis. Avoid intravenous or intra-
arterial administration, or injection into or near a nerve; severe neurovascular damage
(transverse myelitis with permanent paralysis, gangrene requiring amputation, and necrosis
and sloughing at or around injection site) has occurred, especially in infants. Quadriceps
femoris fibrosis and atrophy have occurred following repeated intramuscular administration
into the anterolateral thigh.
Black Box Warning
Inadvertent IV administration of penicillin G benzathine (to be given IM only) has been

associated with cardiorespiratory arrest and death [3].
Pharmacology
Inhibits synthesis of bacterial cell wall. Dissolves slowly at site of injection with hydrolysis to
penicillin G. Distributes widely into body tissues. Highest concentration in the kidneys, with
smaller amounts in the liver, skin, and intestines. Approximately 60% bound to serum
protein. Excreted rapidly by tubular excretion. In young infants and patients with renal
impairment, excretion is prolonged.
603
ABOUT
Available in a concentration of 600,000 units/mL in 1-, 2-, and 4-mL syringes. Store in
refrigerator. Do not freeze.
604
Penicillin G procaine
Dose
Congenital Syphilis: 50,000 units/kg/dose IM once daily for 10 days [1].
Uses
Treatment of congenital syphilis in infants during the first month of life[1]:

Proven or highly probable
an abnormal physical examination consistent with congenital syphilis;
a serum quantitative nontreponemal serologic titer that is fourfold higher than the
mother's titer; OR
a positive darkfield test of body fluid(s).
Possible (normal physical examination and a serum quantitative nontreponemal titer the
same or less than fourfold the maternal titer) and the:
received treatment;
mother was treated with erythromycin or another non-penicillin regimen; OR
mother received treatment less than 4 weeks before delivery.

Congenital Syphilis
Penicillin G
probable)
N/A
Congenital Syphilis
(less likely)
Consider benzathine
occurs
Congenital Syphilis
Administration
605
For IM injection only. Avoid injection into or near an artery or nerve. Administer by
deep IM injection in the midlateral aspect of the thigh. Rotate injection site for repeated
administration. Needle may be blocked if injection is not made at a slow, steady rate due to
high concentration of suspended material in the product.
MEDICATION SAFETY
Adverse Effects
Serious and potentially fatal hypersensitivity reactions have occurred. Avoid intravenous or
intra-arterial administration, or injection into or near a nerve; severe neurovascular damage
(transverse myelitis with permanent paralysis, gangrene requiring amputation, and necrosis
and sloughing at or around injection site) has occurred, especially in infants. Quadriceps
femoris fibrosis and atrophy have occurred following repeated intramuscular administration
into the anterolateral thigh. Prolonged therapy may lead to an increased risk of neutropenia
and serum sickness-like reactions.
Monitoring
Periodic monitoring of CBC and renal function is recommended.
Pharmacology
Inhibits synthesis of bacterial cell wall. Equimolecular compound of procaine and penicillin G
in a suspension. Dissolves slowly at site of injection, with maximum blood level at
approximately 4 hours, declining slowly over a period of 15 to 20 hours. Distributes widely
into body tissues. Highest concentration in the kidneys, with smaller amounts in the liver,
skin, and intestines. Approximately 60% bound to serum protein. Excreted rapidly by tubular
excretion. In young infants and patients with renal impairment, excretion is prolonged.
Approximately 60% to 90% of a dose is excreted in the urine within 24 to 36 hours.
ABOUT
Available in a concentration of 600,000 units/mL in 1-, 2-, and 4-mL syringes. Store in
refrigerator. Do not freeze..
606
607
Penicillin G
Dose
»Use only aqueous crystalline penicillin G for IV administration«
Anthrax: (as part of combination or triple therapy) [1]

32 up to 34 week gestational age
0 to 1 week of age: 100,000 units/kg/dose IV every 12 hours
1 to 4 weeks of age: 100,000 units/kg/dose IV every 8 hours
0 to 1 week of age: 100,000 units/kg/dose IV every 8 hours
1 to 4 weeks of age: 100,000 units/kg/dose IV every 6 hours
Congenital Syphilis: 50,000 units/kg/dose IV over 15 minutes, given every 12 hours during
the first 7 days of life, and every 8 hours thereafter for a total of 10 days [2].
Group B Streptococcal Bacteremia (Definitive Therapy) (Confirmed Early-and Late-

Onset)
Preterm and Full-term
7 days and younger: 50,000 units/kg/dose IV every 12 hours for 10 days when there is no
focus; may increase duration for prolonged or complicated course [3].
8 days and older: 50,000 units/kg/dose IV every 8 hours for 10 days when there is no
focus; may increase duration for prolonged or complicated course [3].
Group B Streptococcal Meningitis (Definitive Therapy) (Confirmed Early-and Late-

Onset)
Preterm and Full-term
7 days or younger: 150,000 units/kg/dose IV every 8 hours for 14 days for uncomplicated
meningitis; may increase duration for prolonged or complicated course [3].
8 days or older: 125,000 units/kg/dose IV every 6 hours for 14 days for uncomplicated
meningitis; may increase duration for prolonged or complicated course [3].
Other susceptible organisms

Bacteremia: 25,000 to 50,000 units/kg/dose IV infusion over 15 minutes, or IM.
Meningitis: 75,000 to 100,000 units/kg/dose IV infusion over 30 minutes, or IM.

0 to 28 12
≤29
>28 8
30 to 36 0 to 14 12
https://www.micromedexsolutions.com/micromedex2/librarian/CS/54E2E6/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/7
608
>14 8
0 to 7 12
37 to 44
>7 8
≥45 ALL 6
Uses
Serious infections (bacteremia and meningitis) due to susceptible strains of

streptococci (non enterococcal).
Congenital syphilis. For congenital syphilis, aqueous crystalline penicillin G is

recommended in neonates with proven or highly probable disease and [2]:
an abnormal physical examination consistent with congenital syphilis;
a serum quantitative nontreponemal serologic titer that is fourfold higher than the
mother's titer; OR
a positive darkfield test (or polymerase chain reaction) of body fluid(s) or lesions
Also recommended in neonates who have a normal physical examination and a serum
quantitative nontreponemal titer the same or less than fourfold the maternal titer and the:
received treatment;
mother was treated with erythromycin or another non-penicillin G regimen; OR
mother received treatment less than 4 weeks before delivery

Congenital Syphilis
Penicillin G
probable)
N/A
Congenital Syphilis
(less likely)
Consider benzathine
occurs
Congenital Syphilis
Group B Streptococcal (GBS) Disease

Definitive: The preferred antibiotic for early-onset and late-onset, culture confirmed-GBS
disease is penicillin G and the alternative is ampicillin [3].

https://doi.org/10.1161/CIR.0000000000000298

609
Streptococci
CefTRIAXone +
gentamicin (not for
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)
Baltimore, 2015
610
Anthrax[1]:

Plus
ruled out) (IV)
Triple IV Therapy
moxifloxacin
Plus
(alternative).
Plus
Administration
Intravenous: Administer by IV intermittent infusion over 15 to 60 minutes at a

concentration of 100,000 to 500,000 units/mL. Penicillin sodium contains 1.68 mEq
sodium/million units and penicillin potassium contains 1.68 mEq potassium/million units and
0.3 mEq sodium/million units [4][5][6].
MEDICATION SAFETY
Adverse Effects
Cardiac arrest has been reported in patients who received high doses infused rapidly.
Significant CNS toxicity has been reported in adults with renal failure who developed CSF
concentrations greater than 10 mcg/mL. Bone marrow depression, granulocytopenia, and
hepatitis are rare. Hypersensitivity has not been seen in neonates.
611
D5W, D10W, and NS.
Acyclovir, amikacin, amiodarone, caffeine citrate, calcium chloride, calcium gluconate,

cefotaxime, cefoxitin, chloramphenicol, cimetidine, clindamycin, dopamine, enalaprilat,
erythromycin lactobionate, esmolol, fluconazole, furosemide, gentamicin, heparin,
hydrocortisone succinate, lidocaine, magnesium sulfate, metronidazole, morphine,
nicardipine, potassium chloride, prostaglandin E1, ranitidine and sodium bicarbonate.
Aminophylline, amphotericin B, metoclopramide, netilmicin, pentobarbital, phenytoin, and

tobramycin.
Monitoring
Follow serum sodium and potassium when using high doses and in patients with renal failure.
Observe IV site for signs of extravasation.
Pharmacology
Mechanism of Action: Inhibits synthesis of bacterial cell wall.
Distribution: Distributed widely to the lung, liver, kidney, muscle, bone, and placenta.
Cerebrospinal fluid penetration is poor, except in inflamed meninges [4].
Excretion: Excreted unchanged in the urine (58% to 85% of dose) [4].
Half-life: Serum half-life correlates inversely with age. In infants 14 days and older, serum
half-life is approximately 1.4 hours [4].
Gestational
Dosage Vd Clearance Half-life Reference
Age
25,000 international units/kg IV 0.64 L/kg 0.09 L/hr/kg 4.6 hours
28 weeks or every 12 hours (n=9) (median) (median) (median) Metsvaht,
younger 50,000 international units/kg IV 0.41 L/kg 0.07 L/hr/kg 3.8 hours 2007
every 12 hours (n=8) (median) (median) (median)
26 to 32 50,000 international units/kg IV 0.54 L 0.103 L/hr 3.9 hours Muller,
weeks every 12 hours (n=20) (mean) (mean) (mean) 2007
32 weeks or 25,000 international units/kg 0.48 L/kg 0.21 L/hr/kg 3.5 hours Padari,
612
older (n=12) (median) (median) (median) 2018
0.63 L/kg 0.25 L/hr/kg 4.2 hours
50,000 international units/kg (n=4)
(median) (median) (median)
[8][9][10]
Gestational Median Median Cmax Median AUC(0 to

Dosage Reference
Age Cmin (mg/L) 12 hours)
25,000 international units/kg IV 3.4
58.9 mg/L 161.2 mg x hr/L
28 weeks or every 12 hours (n=9) mg/L Metsvaht,
younger 50,000 international units/kg every 7.1 2007
145.5 mg/L 389.3 mg x hr/L
12 hours (n=8) mg/L
25,000 international units/kg 3.3
62.5 mg/L 173.6 mg x hr/L
32 weeks or (n=12) mg/L Padari,
older 50,000 international units/kg 6.4 2018
94.5 mg/L 225.1 mg x hr/L
(n=4) mg/L
[8][9]
Penicillin G 50,000 units/kg IV every 12 hours achieved the target concentration in dose
simulations of neonates 26 3/7 to 32 0/7 gestational age at 3 days of life. The target
concentration was defined as the free penicillin G concentration above a MIC of 4 mg/L or
less for at least 50% of the time in 100% of preterm neonates [10].
Hypothermia Penicillin G dosages of 75,000 units/kg/day IV divided every 8 hours for

gestational age (GA) of 36 to 37 weeks, 150,000 units/kg/day IV divided every 8 hours for
GA 38 to 41 weeks, and 200,000 units/kg/day IV divided every 6 hours for GA 42 weeks or
more in neonates (younger than 6 hours) undergoing whole-body cooling for hypoxic-
ischemic encephalopathy achieved target concentrations in dose simulations. The target
concentration was free penicillin G concentration exceeding a MIC of 1 mg/L for at least 50%
of the dosing interval for 90% or more of the simulated infants. Peak concentrations were
targeted below 100 mg/L. The temperature for hypothermia was 33.5° C for 72 hours, then
rewarmed 0.4° C/hr to normothermia (37° C) [11].
ABOUT
Aqueous penicillin G is available as powder for injection in two salt forms: penicillin G
potassium and penicillin G sodium. Penicillin G potassium contains 1.68 mEq (65.6 mg)
potassium per 1 million units, and 0.3 mEq (6.8 mg) sodium per 1 million units. Penicillin G
sodium contains 1.68 mEq (38.6 mg) sodium per 1 million units. Reconstitute the 5-million
unit vial with 8 mL sterile water for injection to make a final concentration of 500,000
units/mL. Reconstituted solution good for 7 days refrigerated. A 100,000 unit/mL dilution
may be made by adding 10 mL of reconstituted solution to 40 mL sterile water for injection.
Dilution stable for 7 days refrigerated. Penicillin G sodium reconstituted solution stable for 3
days in refrigerator.
Penicillin G potassium is also available as a premixed frozen iso-osmotic solution containing
1, 2 or 3 million units in 50 mL.
Note: Penicillin G is also known as benzylpenicillin. Do not confuse with
613
benzathine penicillin which is used only for IM injection. 1 million units is the
equivalent of 600 mg.
614
PENTobarbital
Dose
2 to 6 mg/kg IV.
Uses
Sedative/hypnotic, for short-term use.
Administration
IV: For sedation doses, administer IV over 30 seconds to 2 minutes undiluted (50 mg/mL)
[1][2][3]. May dilute to 5 mg/mL.
MEDICATION SAFETY
Adverse Effects
Respiratory depression. Tolerance, dependence, and cardiovascular depression occur with

continued use. Enhances metabolism of phenytoin, sodium valproate, and corticosteroids by
microsomal enzyme induction.
Black Box Warning
There are serious risks, including profound sedation, respiratory depression, coma, and/or
death, associated with combined use of opioids and benzodiazepines, other drugs that
depress the CNS, or alcohol. Concomitant use should be reserved for patients with no
alternative treatment. If necessary, use the lowest initial dose and titrate based on clinical
response. Monitor patients closely for sedation and respiratory depression. Screen patients
for risk of substance-use disorders [4].
615
D5W, D10W, and NS.
Acyclovir, amikacin, aminophylline, atropine, calcium chloride, chloramphenicol, erythromycin

lactobionate, hyaluronidase, insulin, lidocaine, linezolid, neostigmine, and propofol.
Fat emulsion. Cimetidine, fentanyl, hydrocortisone succinate, midazolam, morphine,

pancuronium bromide, penicillin G, phenytoin, ranitidine, and vancomycin. No data are
currently available on heparin and potassium chloride.
Monitoring
Monitor respiratory status and blood pressure closely.

Serum concentration for sedation: 0.5 to 3 mcg/mL.
Pharmacology
Short-acting barbiturate. PENTobarbital has no analgesic effects. Serum half-life is dose-

dependent (15 to 50 hours in adults) and unknown in neonates. Metabolized by hepatic
microsomal enzyme system.
ABOUT
Injection
Available: 50-mg/mL solution in 20 mL and 50 mL multidose vials. Solution contains
propylene glycol 40%, and alcohol 10%. Irritating to veins; pH is 9.5.
A 5-mg/mL dilution may be made by adding 1 mL of the 50-mg/mL solution to 9 mL of
preservative-free normal saline. Use immediately.
Stability: At least 95% of the initial concentration of PENTobarbital remained on day 100
when PENTobarbital 50 mg/mL was stored at room temperature in polypropylene syringes
[5].
616
617
PHENobarbital
Dose
Anticonvulsant:
Loading dose: 20 mg/kg IV [1][2]. Give additional doses of 10 mg/kg/dose as required
every 20 to 30 minutes up to a total dose of 40 mg/kg [1].
Maintenance: 3 to 5 mg/kg/day IV in 1 to 2 divided doses started 12 hours after the
loading dose [1].
PHENobarbital can also be administered orally or intramuscularly [3][4].
Very low birth weight (less than 1500 g), preterm infants, may require lower
loading doses of less than 15 mg/kg IV followed by single injection of less than 3
mg/kg/day 24 hours later [5].
Neonatal Abstinence Syndrome:

Loading dose: 16 mg/kg orally on day 1 [6][7][8].
Maintenance: 1 to 4 mg/kg/dose orally every 12 hours [6][7][8].
Based on abstinence scoring, weaning can be achieved by decreasing dose 20% every other
day.
Uses
Anticonvulsant: PHENobarbital is the first-line agent for neonatal seizures. The second-line
agents, when seizures are not controlled with the maximal tolerated dose of PHENobarbital,
are a benzodiazepine, phenytoin, or lidocaine [1][12]. PHENobarbital reduced electrographic
seizure burden within 1 hour of administration and for a duration of up to 4 hours (n=19)
[2].
Cholestasis: During first course therapy, ursodiol reduced direct bilirubin by 1.89 mg/dL
compared with an increase of 0.76 mg/dL (p = 0.03) for PHENobarbital in a retrospective
study of 68 preterm and term newborns with direct bilirubin greater than 3 mg/dL. The
change for all treatment courses were -3.96 mg/dL for ursodiol and +0.28 mg/dL for
PHENobarbital. Median dosages were ursodiol 27.43 mg/kg/day enterally and PHENobarbital
4.48 mg/kg/day IV [13].
Neonatal abstinence syndrome (NAS) in nonopiate- or polydrug-exposed infants [6][7]

[8]. In a prospective, randomized, open-label trial, infants 35 weeks gestational age or older
treated with morphine for NAS experienced shorter morphine treatment days (4.6 less days
(95% CI, 0.3 to 8.9 days)) and no difference in morphine total dose with adjunctive
PHENobarbital compared with cloNIDine. However, the total duration of PHENobarbital
therapy continued for an average of 3.8 months (range 1 to 8 months) [14].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/51D010/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
618
May enhance bile excretion in patients with cholestasis before 99Tc-IDA scanning.
Administration
Intravenous: Administer IV over 15 to 30 minutes at a concentration of 10 mg/mL or 65

mg/mL [9]. PHENobarbital sodium can be diluted to 10 mg/mL in normal saline prior to
administration [10].
Oral: The intravenous formulation of PHENobarbital, diluted to 10 mg/mL, has been used
orally. An extemporaneous PHENobarbital suspension can also be used to avoid alcohol
content in the PHENobarbital oral and IV solution (See Special Considerations/Preparation)
[11].
MEDICATION SAFETY
Contraindicated in patients with manifest or latent porphyria, marked liver function

impairment, or respiratory disease with dyspnea or obstruction [3].
Adverse Effects
Sedation at serum concentrations above 40 mcg/mL. Respiratory depression at

concentrations above 60 mcg/mL. Irritating to veins - pH is approximately 10 and osmolality
is approximately 15,000 mOsm/kg H2O.
D5W, D10W, and NS.
Amikacin, aminophylline, caffeine citrate, calcium chloride, calcium gluconate, enalaprilat,

fentanyl, fosphenytoin, heparin, ibuprofen lysine, linezolid, meropenem, methadone,
morphine, propofol, and sodium bicarbonate.

619
Fat emulsion. Hydralazine, hydrocortisone succinate, insulin, methadone, pancuronium,
ranitidine, and vancomycin. No data available on potassium chloride.
Monitoring
PHENobarbital monotherapy will control seizures in 43% to 85% of affected neonates -

adding a second drug (phenytoin or lorazepam) is often needed. Therapeutic serum
concentration is 15 to 40 mcg/mL. Drug accumulation may occur using recommended
maintenance dose during the first two weeks of life. Altered (usually increased) serum
concentrations may occur in patients also receiving phenytoin or valproate. Observe IV site
for signs of extravasation and phlebitis. In infants with neonatal abstinence syndrome, serum
concentrations of 20 to 30 mcg/mL are associated with adequate symptom control.
Pharmacology
PHENobarbital limits the spread of seizure activity, possibly by increasing inhibitory

neurotransmission. Approximately 30% protein bound. Primarily metabolized by liver, then
excreted in the urine as p-hydroxyphenobarbital (no anticonvulsant activity).
A pilot study in 24 preterm infants (weight, less than 1500 g) administered a loading dose of
PHENobarbital 15 mg/kg IV followed by 3 mg/kg/day 24 hours later, demonstrated that
PHENobarbital concentrations were above 40 mcg/mL in 0%, 4.7%, 45.8%, 62.5%, and
70.8% of infants at 2-hours, 24-hours, 48-hours, 72-hours, and 96-hours after the
administration of PHENobarbital [5].
Vd: 0.64 to 1.17 L/kg in neonates [17].
Clearance: 0.0053 to 0.0141 L/hr/kg in neonates [17].
Half-life: 73.9 to 154.5 hours in neonates [17].
Extracorporeal Membrane Oxygenation (ECMO): Based on observed pharmacokinetic

data in 7 neonates (median weight 3.5 kg) and 9 infants (median weight 8 kg) on ECMO, a
simulation for PHENobarbital was suggested. For a loading dose of 15 mg/kg, 68.7% of
neonates and infants were predicted to have PHENobarbital serum concentration between 10
to 40 mg/L and 31.2% would have concentrations above 40 mg/L. For a maintenance dose
of 4 mg/kg/day, 87.5% of neonates and infants were predicted to have PHENobarbital serum
concentration between 10 to 40 mg/L and 12.5% would have concentrations above 40 mg/L.
The following were the pharmacokinetic parameters for PHENobarbital in 7 neonates on
ECMO [18]
Vd: mean, 0.46 L/kg (interquartile range 0.32 to 0.64 L/kg) [18]
CL: mean, 8 mL/kg/hr (interquartile range 5.2 to 9.3 L/kg/hr) [18]
Half-life: 46.1 hours (interquartile range 30.7 to 51.7 hours) [18]
ABOUT
620
Injection: Injectable solution available in concentrations of 60-, 65-, and 130-mg/mL, all
containing 10% (100 mg/mL) alcohol and 67.8% propylene glycol. PHENobarbital sodium,
diluted to 10 mg/mL in normal saline, was stable for 4 weeks under refrigeration [10].
Oral: Oral solution is available in 20 mg/5 mL (4 mg/mL) concentration; contains 13.5 %
alcohol.
Extemporaneous Oral Suspension (10 mg/mL): To avoid alcohol content of the oral
solution, an extemporaneous PHENobarbital suspension can be compounded by crushing ten
(10) 60-mg tablets (600 mg total) into a fine powder. Mix 30 mL of Ora-Plus with 30 mL of
either Ora-Sweet or Ora-Sweet SF. Add 15 mL to PHENobarbital powder and triturate.
Transfer suspension to 2-ounce amber plastic bottle and fill to final volume of 60 mL with
Ora-Plus/Ora-Sweet mixture. Label "shake well before use"; suspension stable for 115 days
at room temperature [11].
621
Phentolamine
Dose
Inject a 0.5-mg/mL solution of phentolamine subcutaneously into the affected area. Usual
amount needed is 1 to 5 mL, depending on the size of the infiltrate. May be repeated if
necessary.
Uses
Prevention of dermal necrosis and sloughing caused by extravasation of vasoconstrictive

agents, eg, dopamine.
MEDICATION SAFETY
Adverse Effects
Hypotension could potentially occur if a very large dose is administered. Consider using
topical 2% nitroglycerin ointment if affected extremity is significantly swollen.
Amiodarone, dobutamine, and papaverine.
Monitoring
Assess affected area for reversal of ischemia. Monitor blood pressure.
Pharmacology
Alpha-adrenergic blocking agent that produces peripheral vasodilation, thereby reversing

ischemia produced by vasopressor infiltration. The effect should be seen almost immediately.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/0FFF26/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/2
622
Biological half-life when injected subcutaneously is less than 20 minutes.
ABOUT
Available in 5-mg vial as a lyophilized powder.

To prepare:
1) Reconstitute one vial with 1 mL of normal saline.
2) Dilute to a concentration of 0.5 mg/mL with 9 mL normal saline. Use immediately.
Do not use if solution is discolored or contains particulate contamination.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/0FFF26/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 2/2
623
Phenylephrine (Ophthalmic)
Dose
1 drop instilled in the eye at least 10 minutes prior to funduscopic procedures.

Use only the 2.5% ophthalmic solution in neonates.
Apply pressure to the lacrimal sac during and for 2 minutes after instillation to minimize
systemic absorption.
Uses
Induction of mydriasis for diagnostic and therapeutic ophthalmic procedures.
MEDICATION SAFETY
Adverse Effects
May cause decreased pulmonary compliance, tidal volume, and peak air flow in babies with
BPD. Do not use in patients receiving beta-blocker medications (e.g. propranolol). The use of
10% solutions has caused systemic hypertension and tachycardia in infants.
Monitoring
Monitor heart rate and oxygen saturation in babies with BPD.
Pharmacology
Alpha-adrenergic. Mydriasis begins within 5 minutes of instillation and lasts for 60 minutes.
Without lacrimal sac occlusion, approximately 80% of each drop may pass through the
nasolacrimal system and be available for rapid systemic absorption by the nasal mucosa.
ABOUT
624
Supplied as ophthalmic solution in 0.12%, 2.5%, and 10% concentrations in 2 to 15 mL

quantities. Do not use solution that becomes discolored or contains precipitate. Refer to
specific product or manufacturer's recommendation for storage.
A preparation containing cyclopentolate 0.2% and phenylephrine 1% (Cyclomydril®) is

commercially available in 2- and 8-mL Drop-tainers.
A combination eye drop solution ("Caputo drops") may be prepared in a 15-mL bottle with
3.75 mL of cyclopentolate 2%, 7.5 mL of tropicamide 1%, and 3.75 mL of phenylephrine
10%. The final solution contains cyclopentolate 0.5%, tropicamide 0.5%, and phenylephrine
2.5%.
Use within 24 hours, as the solution contains no preservatives.
625
Phenytoin
Dose
Loading dose: 15 to 20 mg/kg IV infusion.

Maintenance dose: 4 to 8 mg/kg every 24 hours IV slow push, or orally.
(Up to 8 mg/kg per dose every 8 to 12 hours after 1 week of age).
Dosage Adjustment
Pharmacogenomics
CYP2C9 intermediate or poor metabolizer: Reduce dose. No specific recommendations
in pediatric patients; in adults the starting maintenance dose should be reduced by at least
25% in intermediate metabolizers and at least 50% in poor metabolizers. Dose adjustments
are based on target phenytoin concentrations [1].
HLA-B*15:02 carrier: If phenytoin-naive, do not use [1].
HLA-B*15:02 noncarrier with normal CYP2C9 genotype: No dosage adjustment
necessary [1].
Uses
Anticonvulsant often used to treat seizures refractory to phenobarbital.
Administration
Intravenous: Administer directly into a large peripheral or central vein through a large-
gauge catheter. Administer 50 mg/mL (undiluted) at a rate of 1 mg/kg/minute (over
approximately 15 to 20 minutes for loading dose and 10 minutes for maintenance dose). May
dilute in normal saline at a concentration of no less than 5 mg/mL and infuse within 1 to 4
hours (60 to 240 minutes). If diluted in normal saline, then use an in-line filter (0.22 to 0.55
microns). Flush IV with saline before and after administration. Always inspect for particulate
matter and discoloration before administration [2][3].
SubQ or perivascular injection should be avoided [4].
IM route not acceptable: poorly absorbed with drug crystallization in muscle; may cause
necrosis of soft tissues at the injection site [5].
National Institute for Occupational Safety and Health (NIOSH) Recommendations

In the preparation and administration of injections, the National Institute for Occupational
Safety and Health (NIOSH) recommends the use of double gloves and a protective gown.
Prepare in a biological safety cabinet or a compounding aseptic containment isolator;
eye/face and respiratory protection may be needed. Prepare compounds in a closed system
drug transfer device. During administration, if there is a potential that the substance could
splash or if the patient may resist, use eye/face protection. Administer certain dosage forms
via a closed system drug transfer device [6].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/2E5E1C/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/6
626
[6].
Extravasation ManagementNeonatal data are limited to pooled data from 10 case

reports/case series (n=237) and are not specific to phenytoin extravasation; subcutaneous
saline irrigation with or without hyaluronidase infiltration was commonly used. No
standardized management was established. An option for more severe injuries (stages 3 and
4) is subcutaneous irrigation with saline, but this is not advocated as standard treatment.
Conservative management is appropriate for mild extravasation (stages 1 and 2) [7].
Although not neonatal-specific, the following are recommendations for extravasation of acidic
or alkaline agents (phenytoin is alkaline with a pH of 10 to 12, greater than 700 mOsm/L) [8]
General:
Stop and disconnect infusion; do not remove the cannula or needle
Attempt to gently aspirate as much extravasated agent as possible; avoid manual
pressure
Remove cannula or needle
Dry heat and elevation
Closely monitor for signs of coagulation and ischemia
Avoid attempt at pH neutralization (phenytoin - pH 10 to 12)
Alternate treatment, topical nitroglycerin 2% apply up to 1-inch strip to affected area
every 8 hours as needed. Hypotension may occur as dosage may exceed those typically
used for angina
Monitor and consider the need for surgical management such as surgical flushing with
normal saline or debridement and excision of necrotic tissue (especially if pain persists
for 1 to 2 weeks). In cases of compartment syndrome, surgical decompression may be
required
Refractory Events:
Hyaluronidase 15 units intradermally along injection site and edematous area. Give as
five, 0.2-mL intradermal injections along extravasation site and edematous tissue.
Inadvertent Intraarterial Administration:
Leave inadvertent intraarterial line in place for diagnostics
Systemic heparin titrated to therapeutic anticoagulant effect.
Stellate ganglion block
MEDICATION SAFETY
627
Contraindications
•Coadministration with delavirdine due to the potential for loss of virologic response and
possible resistance to delavirdine or the class of NNRTI [11][12]
•History of prior acute hepatotoxicity attributable to phenytoin [11][12]
•History of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [11]
[12].
Precautions
Cardiovascular: Bradycardia and cardiac arrest, including cases at recommended doses and
phenytoin levels and those associated with toxicity, have been reported; cardiac arrest has
occurred mostly in patients with underlying cardiac disease [13]
Concomitant use: Concomitant use of oral phenytoin with enteral feeding preparations not
recommended [10][14][15].
Dermatologic: Soft tissue irritation and inflammation varying from slight injection site
tenderness to extensive necrosis and sloughing, including "purple glove syndrome" with
edema, discoloration, and pain distal to injection site, have been reported (even without
extravasation); fasciotomies, skin grafting, or amputation may be necessary [10].
Dermatologic: Severe cutaneous reactions, including fatalities (eg, acute generalized
exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal
necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms [DRESS]) have
been reported; discontinue use at the first sign of rash, unless clearly not drug-related, and
evaluate patients for severe cutaneous reaction; do not reinitiate therapy if signs or
symptoms suggest severe cutaneous reaction [13][12]
Dermatologic: Presence of HLA-B*1502 allele (more common in patients of Asian ancestry)
may increase risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis in
patients taking antiepileptic drugs, including phenytoin; consider avoiding phenytoin as a
carbamazepine alternative in patients positive for HLA-B*1502 [13][14]
Endocrine and metabolic: Hyperglycemia has been reported [10][16][14][15].
Endocrine and metabolic: Serum glucose levels may increase in patients with diabetes
[10][16][14][15].
Hematologic: Thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and
pancytopenia with or without bone marrow suppression, including fatal cases, have been
reported [10][16][14][15].
Hematologic: Use caution in patients with porphyria as exacerbation has been reported
[10][16][14][15].
Hepatic: hyperbilirubinemia; bilirubin displaces phenytoin from protein-binding sites,
resulting in increased serum free phenytoin concentration [17].
Hepatic: Patients with hepatic disease have an increased fraction of unbound phenytoin;
interpret total phenytoin plasma concentrations with caution [10].
Hepatic: Acute hepatotoxicity, including hepatic failure and fatalities, has been reported;
discontinue and do not re-administer [10][16][14][15].
Hepatic: Phenytoin toxicity may occur in patients with impaired liver function or those who
are gravely ill [10][16][14][15].
Immunologic: Drug reaction with eosinophilia and systemic symptoms (DRESS), also
known as multiorgan hypersensitivity, including fatal cases, has been reported; evaluate
patient if signs and symptoms are present and discontinue phenytoin if alternative etiology
cannot be established [10][16][14][15].
Immunologic: Angioedema has been reported; discontinue immediately for presence of
symptoms (facial, perioral, or upper airway swelling) [13][12]
Immunologic: Consider alternatives to structurally similar drugs such as carboxamides,
barbiturates, succinimides, and oxazolidinediones in patients with a history of hypersensitivity
628
to phenytoin [10][16][14][15].
Immunologic: Consider alternative to phenytoin in patients with personal or immediate
family history of hypersensitivity to structurally similar drugs [10][16][14][15].
Immunologic: Local and generalized lymphadenopathy may occur; extended follow-up is
recommended in all cases and alternative antiepileptic therapy should be utilized if possible
[10][16][14][15].
Musculoskeletal: Decreased bone density and bone fractures have been reported, possibly
due to increased metabolism of vitamin D and vitamin D deficiency; consider screening and
initiating treatment if detected [16][14][15].
Neurologic: Dose-related CNS toxicity may occur in slow metabolizers; check plasma levels
immediately if signs of toxicity develop [16][14][15].
Neurologic: Delirium, psychosis, encephalopathy, or rarely irreversible cerebellar
dysfunction may occur with concentrations above the therapeutic range; recommend plasma
phenytoin levels at first sign of toxicity and dose reduction if excessive [10][16][14][15].
Pregnancy: A potentially life-threatening bleeding disorder may occur in neonates exposed
to phenytoin in utero; administer vitamin K to mother prior to delivery and to neonate after
birth [10][16].
Renal: Patients with renal disease have an increased fraction of unbound phenytoin;
interpret total phenytoin plasma concentrations with caution [10].
Special populations: Avoid use in HLA-B*1502 carriers if patient is
phenytoin/fosphenytoin-naive [1]. HLA-B*15:02-positive patients (most common in Asian
patients) may have an increased risk of Stevens-Johnson syndrome and toxic epidermal
necrolysis [18].
Special populations: Dose reduction and monitoring recommended in HLA-B*1502 non-
carriers with intermediate or poor CYP2C9 metabolizer status [1].
Withdrawal: Abrupt withdrawal may precipitate increased seizure activity, status
epilepticus. Dose reduction, discontinuation, or substitution of anticonvulsant therapy should
be done gradually; if rapid withdrawal is necessary due to an allergic or hypersensitivity
reaction, alternative therapy should not be in hydantoin class [10][16][14][15].
Adverse Effects
Extravasation causes tissue inflammation and necrosis due to high pH and osmolality.
Propylene glycol content of the intravenous formulation has been associated with seizures
and may potentiate the cardiovascular effects of phenytoin. Hypotension and cardiac
arrhythmias have been reported. High serum concentrations are associated with seizures.
Dose related adverse events include nystagmus (total level 15 to 25 mg/L) and ataxia and
mental status changes (total level greater than 30 mg/L). Movement disorders (bradykinesia
and choreoathetosis) may also occur rarely. Hypersensitivity reactions have been reported in
infants. Long-term effects of phenytoin include gingival hyperplasia, coarsening of the facies,
hirsutism, hyperglycemia, and hypoinsulinemia. Cutaneous side effects include
maculopapular exanthema, drug-induced lupus, and pigmentary alterations. Phenytoin
interacts with carbamazepine, cimetidine, corticosteroids, digoxin, furosemide, phenobarbital,
and valproate [2][19][5].
Supplementation with folic acid 0.5 mg/day orally was associated with a significantly lower
rate of gingival hyperplasia (21% vs. 87.9% for placebo) in children 6 to 15 years of age
taking phenytoin in a 6-month, randomized, double-blind, placebo controlled study (N=120)
[20].
629
Black Box Warning
The rate of intravenous phenytoin administration should not exceed 1 to 3 mg/kg/min (or 50
mg per minute, whichever is slower) in pediatric patients because of the risk of severe
hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after
administering intravenous phenytoin. Although the risk of cardiovascular toxicity increases
with infusion rates above the recommended infusion rate, these events have also been
reported at or below the recommended infusion rate. Reduction in rate of administration or
discontinuation of dosing may be needed [10].
NS only.
D5W and D10W.
Esmolol, famotidine, and fluconazole.
Amikacin, cefepime, ceftazidime, chloramphenicol, clindamycin, dobutamine, enalaprilat,

fentanyl, heparin, hyaluronidase, hydrocortisone succinate, insulin, lidocaine, linezolid,
methadone, micafungin, morphine, nitroglycerin, pentobarbital, potassium chloride,
procainamide, propofol, sodium bicarbonate, and vitamin K1.
Monitoring
Monitor electrocardiogram, blood pressure, and respiratory function continuously during

infusion, and for 15 minutes to 1 hour after infusion [2][9]. Observe IV site for extravasation.
Follow serum concentration closely: therapeutic range is 6 to 15 mcg/mL in the first weeks,
then 10 to 20 mcg/mL due to changes in protein binding. Obtain initial trough level 48 hours
after IV loading dose.
630
Pharmacology
Hepatic metabolism capacity is limited; saturation may occur within therapeutic range.
Pharmacokinetics are dose-dependent. Elimination rate is increased during first few weeks of
life. Serum half-life is 18 to 60 hours. 85% to 90% protein bound. Bilirubin displaces
phenytoin from protein-binding sites, resulting in increased serum free phenytoin
concentration [21][22][23][17][24].
In neonates, oral and IV phenytoin doses resulted in similar serum concentrations [25].
ABOUT
Injectable solution: 50 mg/mL. Contains 0.4 mL/mL of propylene glycol and 0.1 mL/mL of
alcohol. For IV infusion, dilute in NS to a final concentration of no less than 5 mg/mL. Do not
refrigerate diluted solution [2].
Oral suspension: 25 mg/mL [26].
Extemporaneous Compound
15 mg/mL Oral Suspension [27]
Phenytoin, as an active pharmaceutical ingredient, was compounded with SyrSpend®
SF PH4 to make a 15 mg/mL suspension
Stable for 90 days at refrigeration (2 to 8 degrees C) and room temperature (20 to 25
degrees C)
Shake suspension for 1 minute before measuring dose
631
Piperacillin/Tazobactam
Dose
Dosing in neonates is based on limited pharmacokinetic studies [1][2][3].

PMA
Postnatal Dose IV * † Interval
(weeks)
0 to 28 days 12 hours
29 weeks or less 100 mg/kg/dose
greater than 28 days 8 hours
30 to 36 weeks 100 mg/kg/dose
45 weeks or more ALL 100 mg/kg/dose 8 hours
PMA = Postmenstrual age (PMA equivalent to gestational age plus postnatal age). PMA is the
primary determinant of dosing interval, with postnatal age as the secondary qualifier.
*Dose for piperacillin component
Cohen-Wolkowiez, 2014
† Target concentrations were achieved (unbound piperacillin concentrations for 75% of the
dosing interval) in 78%, 75%, and 90% of dose simulations at MICs of 32 mg/L, 16 mg/L,
and 8 mg/L or less, respectively [2].
Dose Adjustments
Renal impairment
Dosage adjustment is recommended; there are no data available to provide dose
recommendations for neonate patients with renal impairment[4].
Uses

https://doi.org/10.1161/CIR.0000000000000298

Streptococci
Gentamicin (for first enterococci
632
or 2 weeks, or entire Ampicillin +
enterococci course for CefTRIAXone (for
CefTRIAXone +
gentamicin (not for
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)
Baltimore, 2015

Piperacillin/tazobactam is not approved for newborn infants.
In children 2 months or older, it's approved for appendicitis (complicated by rupture or
abscess) and peritonitis caused by piperacillin-resistant, β-lactamase producing strains of
Escherichia coli or the following members of the Bacteroides fragilis
group: , B fragilis B
ovatus B thetaiotaomicron B vulgatus
, , or [4].
Additional approved indications in adults: uncomplicated and complicated skin and skin
633
structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic food
infections caused by β-lactamase producing isolates of Staphylococcus aureus
; postpartum
endometritis or pelvic inflammatory disease caused by β-lactamase producing isolates of E
coli; community-acquired pneumonia (moderate severity only) caused by β-lactamase
Haemophilus influenzae
producing isolates of ; moderate to severe nosocomial pneumonia
caused by β-lactamase producing isolates ofS aureus and by piperacillin/tazobactam-
susceptibleAcinetobacter baumanii H influenzae, Klebsiella pneumoniae
, , and Pseudomonas
aeruginosa ; use concomitant aminoglycoside therapy when treating nosocomial pneumonia
caused by P aeruginosa [4].
Administration
Infuse IV over at least 30 minutes at [5] recommended concentrations in pediatric patients of

40, 60, and 200 mg/mL (piperacillin component) [6].
MEDICATION SAFETY
CONTRAINDICATIONS
Contraindicated in patients with a history of hypersensitivity reactions to any of the
penicillins, cephalosporins, or beta-lactamase inhibitors [4].
PRECAUTIONS
Concomitant Use: Probenecid not recommended unless benefit outweighs risk [4]
Dermatologic: Serious cutaneous reactions (eg, Stevens-Johnson syndrome, toxic
epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and
acute generalized exanthematous pustulosis) have been reported; close monitoring
recommended and discontinue if lesions progress [4]
Endocrine and metabolic: Hypokalemia may occur especially in patients with low
potassium reserves and concomitant diuretic or cytotoxic therapy; monitoring recommended
in patients with low potassium reserves [4]
Endocrine and metabolic: Use caution in patients requiring sodium restriction as product
contains 2.84 mEq (65 mg) of sodium per g of piperacillin [4].
Gastrointestinal: Clostridium difficile-associated diarrhea, including mild diarrhea to fatal
colitis, has been reported and may occur more than 2 months after use; discontinuation of
antibacterial use not directed against C. difficile may be required [4]
Hematologic: Bleeding manifestations have been reported with piperacillin use, especially in
patients with renal failure; monitoring recommended particularly with prolonged use (ie, 21
days or greater); discontinue use if occurs [4]
Hematologic: Leukopenia and neutropenia have been reported, especially with prolonged
use; usually reversible upon discontinuation; however, monitoring recommended [4]
Immunologic: Serious anaphylactic reactions, with some fatal cases, have been reported,
especially in patients with history of penicillin, cephalosporin, or carbapenem hypersensitivity
or history of sensitivity to multiple allergens [4]
Neurologic: Neuromuscular excitability or convulsions may occur at higher than
recommended doses, particularly in the presence of renal failure [8].
Renal: Increased risk of nephrotoxicity in critically ill patients, including renal failure and
634
delayed recovery of renal function; consider alternative therapy, otherwise monitoring
required during treatment [9].
Renal: Use caution in patients with renal failure; increased risk of neuromuscular excitability
or convulsions with higher than recommended IV doses [4]
Renal: Renal insufficiency (ie, CrCl less than or equal to 40 mL/min) and hemodialysis or
continuous ambulatory peritoneal dialysis patients; dosage adjustments required [4]
Respiratory: Use caution in patients with cystic fibrosis due to increased risk for fever and
rash [4]
Adverse Effects
Common adverse events (greater than 5%) in adults were diarrhea, constipation, nausea,
headache, and insomnia [4].
D5W, D10W, NS and LR.
Aminophylline, aztreonam, bumetanide, calcium gluconate, cefepime, cimetidine,

clindamycin, dexamethasone, dopamine, enalaprilat, esmolol, fluconazole, furosemide,
heparin, hydrocortisone succinate, linezolid, lorazepam, magnesium sulfate, metoclopramide,
metronidazole, milrinone, morphine, potassium chloride, ranitidine, remifentanil, sodium
bicarbonate, trimethoprim/sulfamethoxazole, and zidovudine.
Acyclovir, amikacin, amiodarone, amphotericin B, azithromycin, caspofungin, dobutamine,

famotidine, ganciclovir, gentamicin, netilmicin, tobramycin, and vancomycin.
Monitoring
Monitor electrolytes periodically in patients with low potassium reserves. Consider monitoring
electrolytes periodically in patients with potentially low potassium reserves or those receiving
cytotoxic therapy or diuretics. Periodic assessment of hematopoietic function, especially with
prolonged therapy of 21 days or greater [4].
635
Pharmacology
Piperacillin/tazobactam combines the extended-spectrum antibiotic piperacillin with the beta-

lactamase inhibitor tazobactam.
Distribution: Both piperacillin and tazobactam were 30% bound to plasma proteins. Mean
tissue concentrations were typically 50% to 100% of plasma concentrations. In non-inflamed
meninges, distribution of piperacillin and tazobactam into CSF was low [4].
Excretion: Both piperacillin and tazobactam were eliminated by glomerular filtration and
tubular secretion. Piperacillin was excreted rapidly as unchanged drug (68% excreted
unchanged). Tazobactam and its metabolite was eliminated primarily by renal excretion
(80% excreted unchanged) [4].
Neonatal Pharmacokinetics
Gestational Age Postnatal Age CL (L/hr/kg) V (L/kg) Half-life (hours)
younger than 14
0.055 (0.034 to
days 0.42 5.3 (2.1 to 8.6)
0.137)
less than 32 weeks (n=12)
14 days or older 0.116 (0.033 to
0.42 2.5 (2.1 to 8.9)
(n=9) 0.142)
younger than 14
0.104 (0.063 to
days 0.42 2.8 (2.1 to 4.6)
0.142)
32 weeks or more (n=8)
0.42 4.5 (1.7 to 4.7)
(n=3) 0.177)
0.085 (0.033 to
Overall (n=32) 0.42 3.5 (1.7 to 8.9)
0.177)
Data are median (range) population parameter estimate
Clearance of piperacillin/tazobactam is significantly associated with body weight,

postmenstrual age, postnatal age, and serum creatinine [2].
The population parameter estimates for piperacillin in 32 neonates administered
piperacillin/tazobactam 240 mg/kg/day (piperacillin component) IV divided every 8 hours (3
of the oldest infants (14 days or older and 32 weeks or more gestational age) received 300
mg/kg/day) administered over 30 minutes is in the tables below [2]:
Cohort Predicted Piperacillin Concentrations at Steady State
Concentration for Concentration for

Gestational Age Postnatal Age Cmin (mg/L) 75% of the dosing 50% of the dosing
interval (mg/L) interval (mg/L)
younger than 14
days 38.3 (7.4 to 48.4) 51.9 (16.9 to 58.9) 71.1 (38.6 to 75.6)
14 days or older
34.6 (5.5 to 48.4) 48.5 (13.5 to 58.9) 69.1 (33.6 to 75.6)
(n=9)
636
32 weeks or more younger than 14 28 (1.3 to 48.4) 41.9 (4.7 to 58.9) 64.3 (17 to 75.6)
days
(n=8)
14 days or older
31.1 (1.5 to 60.2) 48.2 (5.7 to 73.4) 76.6 (20.7 to 94.5)
(n=3)
Overall (n=32) 30.1 (1.3 to 60.2) 44.1 (4.7 to 73.4) 66.2 (17 to 94.5)
Data are median (range)
Target concentrations were achieved (unbound piperacillin concentrations for 75% of the
dosing interval) in greater than 90% of dose simulations at MICs of less than 8 mg/L up to
32 mg/L with the following dosages 100 mg/kg/dose IV every 8 hours for PMA of 30 weeks
or less, 80 mg/kg/dose IV every 6 hours for PMA of 31 to 35 weeks, and 80 mg/kg/dose IV
every 4 hours for PMA 36 to 49 weeks [2].
Extended-infusion (over 2 to 4 hours) did not improve target concentrations compared with
standard infusion (30 minutes) in a model-based simulation in neonates [2].
ABOUT
Available as powder for injection (containing EDTA and sodium citrate) in 2.25-g, 3.375-g,
and 4.5-g single-dose vials and 40.5 g pharmacy bulk vials. Each vial provides 2 g, 3 g, 4 g,
and 36 g of piperacillin for the 2.25-g, 3.375-g, and 4.5-g single-dose vials and 40.5 g
pharmacy bulk vials [10].
Each 2.25-g, 3.375-g, 4.5-g vial, and 40.5-g bulk vial contains 5.68, 8.52, 11.36 mEq, and
100.4 mEq (130, 195, 260, 2304 mg) of sodium, respectively [10].
Reconstitute Stable for 24 hours at room temperature, 48 hours refrigerated:
2.25 g vial with 10 mL
40.5 g vial with 152 mL (Concentration: 200 mg/mL piperacillin component)
Further dilution required[10]. Recommended concentrations in pediatric patients: 40, 60,

and 200 mg/mL (piperacillin component) [6].
Ambulatory IV infusion pumps. Reconstitute and dilute each dose to a volume of 25 or
37.5 mL with a compatible solution. Stable for 12 hours at room temperature [10].
Also available in Galaxy® containers (containing EDTA and sodium citrate) as 2.25 g/50 mL,
3.375 g/50 mL, and 4.5 g/100 mL [10].
637
Piperacillin
Dose
50 to 100 mg/kg/dose IV infusion or IM.


0 to 28 12
≤29
>28 8
0 to 14 12
30 to 36
>14 8
0 to 7 12
37 to 44
>7 8
≥45 ALL 6
Uses
Semisynthetic penicillin with increased activity against Pseudomonas aeruginosa and many
strains of Klebsiella, Serratia, E coli, Enterobacter, Citrobacter, and Proteus. Also effective
against group B Streptococcus.
Administration
Intravenous: For IV infusion, dilute reconstituted solution to a concentration of less than or

equal to 40 mg/mL and infuse over 30 minutes [1].
MEDICATION SAFETY
Adverse Effects
Eosinophilia. Hyperbilirubinemia. Elevations in ALT, AST, BUN, and serum creatinine.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/8A9833/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
638
D5W, D10W, and NS.
Acyclovir, aminophylline, aztreonam, clindamycin, enalaprilat, esmolol, famotidine, heparin,

hydrocortisone succinate, linezolid, lorazepam, magnesium sulfate, midazolam, milrinone,
morphine, nicardipine, potassium chloride, propofol, ranitidine, remifentanil, and zidovudine.
Amikacin, amiodarone, gentamicin, netilmicin, fluconazole, tobramycin, and vancomycin.
Monitoring
Desired peak serum concentration is approximately 150 mcg/mL.

Desired trough concentration ranges from 15 to 50 mcg/mL (available as bioassay). Peak
serum concentration is lower with IM administration. Observe IV site for signs of
extravasation.
Pharmacology
Piperacillin is a potent, broad-spectrum, semi-synthetic, ureidopenicillin possessing high

activity against gram-negative bacteria. Inactivation by beta-lactamase-producing bacteria.
Synergistic with aminoglycosides. Good penetration into bone; CSF penetration similar to that
of other penicillins. Serum half-life depends on gestational age and postnatal age. Primarily
excreted renally unchanged.
ABOUT
639
Available as powder for injection in 2-g, 3-g, 4-g, and 40-g vials. Reconstitute 2-g vial with
10 mL of sterile water for injection to make a final concentration of 200 mg/mL.
Reconstituted solution stable for 24 hours at room temperature, 2 days refrigerated. A 50
mg/mL dilution may be made by adding 2.5 mL of reconstituted solution to 7.5 mL sterile
water for injection. Dilution stable for 2 days refrigerated.
IM Administration : Use 400 mg/mL concentration.
640
Poractant alfa
Dose
Respiratory Distress Syndrome

Initial dose: 2.5 mL/kg/dose (200 mg/kg/dose) intratracheally, administered as 1 or 2
aliquots depending upon the instillation procedure [1]
May be followed by up to 2 subsequent doses of 1.25 mL/kg/dose (100 mg/kg/dose)
administered approximately every 12 hours if needed [1]; typically administer no more
frequently than every 12 hours, unless surfactant is being inactivated by an infectious
process, meconium, or blood [2]. For rescue therapy, administer as soon as possible,
preferably within 2 hours after birth. For prophylactic therapy, administer after initial
resuscitation but within 10 to 30 minutes after birth [2].
Maximum dosage: Sum of initial and up to 2 repeat doses, 5 mL/kg (400 mg/kg) [1]
Uses
Respiratory distress syndrome (RDS) in premature infants: It is strongly recommended

that CPAP immediately after birth with subsequent selective surfactant administration be
considered as an alternative to routine intubation with prophylactic or early surfactant
administration in preterm infants. Severe RDS in preterm infants born younger than 30
weeks gestation who need mechanical ventilation should be administered surfactant after
initial stabilization. Consider the use of rescue surfactant for infants with hypoxic respiratory
failure attributable to secondary surfactant deficiency, such as meconium aspiration
syndrome or sepsis/pneumonia[2].
Comparative Trials: Animal-derived surfactants (beractant, calfactant, and poractant alfa)
had comparable outcomes for air leak syndromes, death, and bronchopulmonary dysplasia in
a retrospective study (n=51,282; median birth weight of 1435 g; median gestation age of 30
weeks (27 to 33 weeks)) [3].
Late Administration: Poractant administered at 2 weeks of age in very preterm infants

(less than 33 weeks' gestation) on ventilation did not reduce the duration of ventilation;
however, the rehospitalization rate for respiratory problems after discharge at 1 year of age
was reduced (28.3% vs 51.1%; p=0.03) in a randomized, double-blinded, controlled,
multicenter trial (n=118). The dosage of poractant was 2.5 mL/kg (200 mg/kg) [4].
Neonatal FDA-Approved Indications

Indicated for the treatment (rescue) of respiratory distress syndrome in premature infants.
Poractant alfa reduced mortality and pneumothoraces associated with RDS [1].
Administration
641
For Endotracheal Tube Instillation Using a 5-French end-hole Catheter
•May suction the endotracheal tube before administration of surfactant [1]
•Slowly withdraw the entire contents of the vial into a 3 or 5 mL plastic syringe through a
large-gauge needle (e.g., at least 20 gauge); enter each single-use vial only once [1]
•Attach the 5 French end-hole catheter of appropriate length to position the catheter tip
proximal to the distal portion of the endotracheal tube, to the syringe. Fill the catheter with
poractant alfa suspension. Discard excess poractant alfa through the catheter so that only
the dose to be given remains in the syringe [1]
•First aliquot: Keep infant in neutral position, right or left side dependent. Immediately
before administration, ventilate the infant with supplemental oxygen to maintain SaO(2)
greater than 92%. Insert catheter into the endotracheal tube and instill the first aliquot, then
remove catheter and manually ventilate with supplemental oxygen until stable [1]
•Second aliquot: When the infant is stable, reposition the infant such that the other side is
dependent. Administer the remaining aliquot using the same procedure as the first aliquot.
After completion of the dosing procedure, do not suction airways for 1 hour after surfactant
instillation unless signs of significant airway obstruction occur [1]
For Endotracheal Tube Instillation Using the Second Lumen of a Dual Lumen
Endotracheal Tube without Interrupting Ventilation
•May suction the endotracheal tube before administration of surfactant [1]
•Slowly withdraw the entire contents of the poractant alfa suspension vial into a 3 or 5 mL
plastic syringe through a large-gauge needle (e.g., at least 20 gauge). Do not attach 5
French end-hole catheter. Remove the needle and discard excess poractant alfa suspension
so that only the dose to be given remains in the syringe [1].
•Keep the infant in a neutral position (head and body in alignment without inclination).
Administer poractant alfa suspension through the proximal end of the secondary lumen of
the endotracheal tube as a single dose, given over 1 minute, and without interrupting
mechanical ventilation [1].
•After completion of this dosing procedure, ventilator management may require transient
increases in FiO2 , ventilator rate, or PIP. Do not suction airways for 1 hour after surfactant
instillation unless signs of significant airway obstruction occur [1].
MEDICATION SAFETY
Contraindications
Specific contraindications have not been determined[1]
Precautions
Administration: Transient events (including bradycardia, hypotension, endotracheal tube
blockage, and oxygen desaturation) may occur; stop administration and treat as needed,
when patient is stable may continue dosing with appropriate monitoring [1]
Respiratory: Exogenous surfactants can rapidly affect oxygenation and lung compliance;
monitoring required [1]
Adverse Effects
642
Transient episodes of reflux of bradycardia, hypotension, endotracheal tube blockage, and
oxygen desaturation have been reported during administration [5].
Monitoring
Monitor clinical and laboratory tests frequently for appropriate oxygen therapy and
ventilatory support [5].
Pharmacology
Pulmonary lung surfactants are essential for effective ventilation by modifying alveolar
surface tension thereby stabilizing the alveoli. Curosurf® is an extract of natural porcine lung
surfactant consisting of 99% polar lipids (mainly phospholipids) and 1% hydrophobic low
molecular weight proteins (surfactant associated proteins SP-B and SP-C). Each mL of
surfactant contains 76 mg of phospholipids calculated from the content of phosphorus (55
mg of phosphatidylcholine of which 30 mg is dipalmitoyl phosphatidylcholine) and 1 mg of
protein including 0.45 mg of SP-B and 0.59 mg of SP-C [1].
ABOUT
Availability: 1.5 mL (120 mg poractant alfa) and 3 mL (240 mg poractant alfa) vials [1]
Storage: Refrigerate at 2 to 8 degrees C (36 to 46 degrees F) and protect from light.
Inspect Curosurf® for discoloration; normal color is creamy white. If settling occurs during
storage, gently turn vial upside-down in order to uniformly suspend. Do not shake. Used
vials with residual drug should be discarded. Unopened vials that have been warmed to room
temperature one time may be refrigerated within 24 hours and stored for future use. Should
not be warmed and returned to the refrigerator more than once [1].
Preparation
•Slowly warm vial to room temperature before administration [1]
•Discard if suspension discolored (other than white to creamy white) [1]
•Gently turn vial upside down to obtain a uniform suspension; do not shake [1]
643
Potassium chloride
Dose
Initial oral replacement therapy: 0.5 to 1 mEq/kg/day orally divided and administered
with feedings (small, more frequent aliquots preferred). Adjust dosage based on monitoring
of serum potassium concentrations.
1 g KCl = 13.4 mEq K+1 mEq K+ = 74.6 mg KCl
Acute treatment of symptomatic hypokalemia: Begin with 0.5 to 1 mEq/kg IV over 1

hour, then reassess.
Daily Requirement: 2 to 4 mEq/kg/day IV of potassium [1],
Uses
Treatment of hypokalemia.
Administration
Maximum infusion rate 1 mEq/kg/hour [2][3]. Preferred concentration for peripheral infusion
is 40 mEq/L; maximum concentration for peripheral infusion 60 to 80 mEq/L[2][4]
[5][6][7]. A maximum concentration of 200 mEq/L for central line infusion has been
suggested [8]
MEDICATION SAFETY
Contraindicated in patients with renal failure. Rapid IV infusions, especially concentrated

solutions through central lines, may cause arrhythmias including heart block and cardiac
arrest. Peripheral IV administration of concentrated potassium solutions is associated with
thrombophlebitis and pain at the injection site; central line should be used for concentrated
solutions. Other signs of potassium toxicity include paresthesia of the extremities, weakness,
and mental confusion [9][7].
644
Adverse Effects
GI irritation is common--most commonly diarrhea, vomiting, and bleeding-- minimized by

dividing oral doses and administering with feedings. Use with caution (if at all) in patients
receiving potassium-sparing diuretics, e.g. spironolactone [9][7].
Most standard IV solutions.
Most drugs.
Amphotericin B, diazepam, and phenytoin.
Monitoring
Continuous EKG monitoring is mandatory if administering by the IV route,

especially for central infusions. Observe IV site closely for signs of extravasation when
using concentrated solutions. Monitor serum potassium concentration. Assess for GI
intolerance.
Pharmacology
Potassium is the major intracellular cation. Hypokalemia in critically ill neonates is usually the
result of diuretic (furosemide, thiazides) therapy or diarrhea. Other causes include congenital
adrenal hyperplasia and renal disorders. Alkalosis, as well as insulin infusions, will lower
serum potassium concentrations by driving the ion intracellularly. Symptoms of hypokalemia
include neuromuscular weakness and paralysis, ileus, urine retention, and EKG changes (ST
segment depression, low-voltage T wave, and appearance of U wave). Hypokalemia
increases digitalis toxicity. Oral potassium preparations are completely absorbed.
645
ABOUT
Potassium chloride for injection is supplied as 2-mEq/mL solution. Always dilute before
administration. Hyperosmolar - 4355 mOsm/kg determined by freezing-point depression.
pH ranges from 4 to 8 depending on buffering. Various oral solutions are available, with
concentrations ranging from 10 to 40 mEq per 15 mL. Other oral forms available include
powder packets, tablets, and sustained-release capsules.
646
Potassium Iodide
Dose
Prevent Injury to Thyroid Gland Due to Radiation Emergency

Use under the direction of public officials
[1]
16.25 mg orally every day [1]
Uses
Nuclear Radiation Emergency: Helps prevent radioactive iodine from getting into the
thyroid gland during a nuclear radiation emergency (Thyroshield®)[1].

Safety and effectiveness in children have not been established for saturated solution of
potassium iodide (SSKI®) [2]
MEDICATION SAFETY
Precautions
Cardiac: Use with caution in patients with cardiac disease [2].
Endocrine and Metabolic: May cause overactive thyroid gland, underactive thyroid gland,
or enlargement of thyroid gland (goiter). Newborns are more like to experience an
underactive thyroid gland [1].
Endocrine and Metabolic: Prolonged use can lead to hypothyroidism [2].
Endocrine and Metabolic: Use with caution in patients with Addison's disease or
hyperthyroidism [2].
Musculoskeletal: Use with caution in patients with myotonia congenita [2].
Renal: Use with caution in patients with renal function impairment [2].
Respiratory: Use with caution in patients with tuberculosis or acute bronchitis [2].
Endocrine and Metabolic: Newborns are more like to experience an underactive thyroid
gland [1].
Immunologic: Allergic reactions may occur [1].
Adverse Effects
Swelling or tenderness of salivary glands, nausea, vomiting, diarrhea, stomach ache, fever,
headache, metallic taste, and allergic reactions [1].
647
Pharmacology
Thyroid blocking [1].
ABOUT
Availability: 65 mg/mL potassium iodide oral solution over-the-counter product (used in the
prevention of injury to the tyroid gland due to a radiation emergency) [1]; 1 g/mL of
saturated solution of potassium iodide (SSKI) [2]
Storage: Protect from light [1][2].
648
Procainamide
Dose
Initial bolus dose: 7 to 10 mg/kg IV.
Maintenance IV infusion: 20 to 80 mcg/kg per minute. Premature neonates should

receive the lowest dose.
Uses
Acute treatment of supraventricular tachycardia (SVT) refractory to vagal maneuvers and

adenosine. Acute treatment of ventricular tachycardia unresponsive to cardioversion and
adenosine. Ectopic tachycardia, junctional ectopic tachycardia, and atrial flutter. Consider
obtaining expert consultation before use.
Administration
Intravenous/Intraosseous: Administer loading dose over 30 to 60 minutes at a

concentration of 20 mg/mL. For continuous infusion, administer at a concentration of 2 to 4
mg/mL [1][2][3].
MEDICATION SAFETY
Contraindicated in patients with complete heart block and torsades de pointes [3].
Adverse Effects
Severe hypotension with rapid infusion, bradycardia, A-V block, and ventricular fibrillation
have been reported in adult patients. Normal procainamide concentrations widen the QRS
complex due to slowing of conduction in the Purkinje system and ventricular muscle. The
drug should be discontinued if the QRS duration increases by more than 35 to 50 percent to
avoid serious toxicity. Adverse effects are reversible with discontinuation of drug [7][8][9].
649
Black Box Warning
The use of procainamide hydrochloride as well as other antiarrhythmic agents should be

reserved for patients with life-threatening ventricular arrhythmias. The prolonged
administration of procainamide often leads to the development of a positive ANA test, with or
without symptoms of a lupus erythematosus-like syndrome. Agranulocytosis, bone marrow
depression, neutropenia, hypoplastic anemia, and thrombocytopenia in patients receiving
procainamide hydrochloride have been reported (in adults), some of which were fatal.
Discontinue procainamide if hematologic disorders are identified [3].
D5W (conflicting data), 0.45% NaCl, and NS.
D5W (conflicting data).
Amiodarone, dobutamine, famotidine, flumazenil, heparin, hydrocortisone, lidocaine,

netilmicin, ranitidine, remifentanil, and sodium nitroprusside.
Esmolol, milrinone, and phenytoin.
Monitoring
Continuous monitoring of the EKG, blood pressure and heart rate [1][3]. Measure
procainamide and N-acetyl procainamide (NAPA) concentrations at 2, 12, and 24 hours after
starting the loading dose infusion [4].
Therapeutic concentrations:
Procainamide: 4 to 10 mcg/mL, NAPA 6 to 20 mcg/mL [4][5][6].
Sum of procainamide and NAPA: 10 to 30 mcg/mL [4].
Increasing frequency of toxicity associated with procainamide levels greater than 10 mcg/mL
[3].
650
Pharmacology
Procainamide is a class IA antiarrhythmic agent that increases the effective refractory period
of the atria and the ventricles of the heart. Onset of action occurs within minutes of starting
the loading dose. Half-life is approximately 5 hours in the term neonate, and longer in
preterms. Metabolized primarily (60%) in the liver to N-acetylprocainamide (NAPA), an active
metabolite. The rate of acetylation is primarily genetically determined in adults and children.
Preterm neonates have a higher NAPA:procainamide ratio than term infants presumably due
to delayed excretion of NAPA. Renal function is a significant determinant of procainamide
clearance [4][3][10].
ABOUT
Available in 10-mL vials providing 100 mg/mL or 2-mL vials providing 500 mg/mL. Store at
room temperature. Do not freeze.
Dilute initial bolus dose to a final concentration of 20 mg/mL prior to administration.

Maintenance infusion should be diluted to 2 to 4 mg/mL in compatible solution before
administration [3].
651
Propranolol
Dose
Hypertension and Tachyarrhythmias

Starting oral dose: 0.25 to 1 mg/kg/dose orally every 6 hours [1][2][3].
Increase as needed to maximum of 3.5 mg/kg/dose orally every 6 hours.
Starting IV dose: 0.01 mg/kg/dose IV every 6 hours over 10 minutes.

Increase as needed to maximum of 0.15 mg/kg/dose IV every 6 hours.
Effective dosage requirements will vary significantly.
Infantile Hemangiomas
Not approved in infants younger than 5 weeks[4].
Optimal maintenance dose, timing, and duration have not been established.[5].
Week 1: 0.6 mg/kg/dose orally twice daily, at least 9 hours apart [4].
Week 2: 1.1 mg/kg/dose orally twice daily [4].
Week 3: 1.7 mg/kg/dose orally twice daily for 6 months. Adjust the dose periodically as the
child's weight increases. May re-initiate if hemangiomas recur [4]. 2.3 to 3.4 mg/kg/day was
recommended (guideline dosing) [6].
Continuation of therapy until full involution of the lesion has occurred or until 1 year of age
has been recommended [7], typically continue until at least 8 to 12 months of age
(treatment duration of 3 to 12 months) [5]. Recurrences have been reported with early
discontinuation of therapy [8]. Tapering periods have ranged from 2 weeks to 1 month [9]
[10][11][12][13].
Dose adjustment: In infants with PHACE syndrome (posterior fossa defects, hemangiomas,
cerebrovascular arterial anomalies, cardiovascular anomalies, and eye anomalies), especially
in the presence of neurovascular anomalies, slowly titrate dose, use the lowest effective
dose, and administer in 3 divided doses. Lower doses may also be necessary in patients with
progressive IH ulceration while receiving therapy and in patients who experience adverse
effects (e.g. sleep disturbances) [6].
Uses
Tachyarrhythmias and hypertension. Preferred therapy for supraventricular

tachycardia if associated with Wolff-Parkinson-White syndrome. Palliation of tetralogy of
Fallot and hypertrophic obstructive cardiomyopathy. Adjunctive treatment of
neonatal thyrotoxicosis.
In 287 infants (median age, 17 days), oral propranolol 3.6 +/- 1 mg/kg/day divided every 6
hours controlled 67.3% of arrhythmias (reentrant arrhythmias or atrial tachycardia) in a
retrospective study. The average dose for propranolol monotherapy, which was successful, at
discharge was 4 mg/kg/day. One patient discontinued propranolol due to an adverse event
(bradycardia) [1].
Infantile hemangiomas (IH): The first-line agent for IH requiring systemic treatment is
oral propranolol. Oral prednisoLONE or predniSONE are alternatives when propranolol is
https://www.micromedexsolutions.com/micromedex2/librarian/CS/0F14DB/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/5
652
contraindicated or when there is a lack of response to propranolol. For bulky IH during
proliferation or when critical anatomic locations are involved, then intralesional injection of
triamcinolone and/or betamethasone is recommended. For thin and/or superficial IH, topical
timolol is an option [6]. The strength of evidence is high for the effectiveness of propranolol
for reducing IH lesion size; although, the optimal dosage, timing, and duration of propranolol
therapy, as well as the potential for long-term harm, is not known [15]. The FDA-approved
age for initiation of propranolol is 5 weeks to 5 months based on a randomized, double-blind
study (n=460) [4] and in retrospectives studies (n=124), the age of initiation of treatment
was usually older than 1 month of age; however, neonates have been treated with
propranolol for hemangiomas [16][17]. The mean age of treatment initiation was 9.4 months
(2 to 54 months) in a retrospective study (n=99) [16].
In a randomized study (n=34), propranolol 2 mg/kg/day was noninferior to prednisoLONE 2
mg/kg/day for the proportion of patients with IH (mean age, 3.3 months; range, 0.3 to 8.2
months) who achieved clinical response at 16 weeks (95.65% vs 91.94%, respectively).
There was also no significant difference between propranolol and prednisoLONE for volume
reduction (55.87% vs 46.52%) or median time to progression stop or regression (12 vs 11
days) [18].
In a randomized, double-blind study (n=460), 60% of patients treated with 3 mg/kg/day for
6 months of oral propranolol compared with 4% of placebo-treated patients experienced
complete or nearly complete resolution of IH after 24 weeks of treatment (p less than 0.001).
Re-treatment with propranolol from week 24 to week 96 was necessary in 10% of
propranolol-treated patients [19]. In a multi-center retrospective study (n=980), 25.3% of
the infants experienced rebound growth of IH after a mean duration of 11.4 months of
propranolol [20].
The use of surgical therapy was reduced but not eliminated in propranolol treated pediatric
patients with nasal IH in a retrospective study (n=58) [17].
Pediatric FDA Approved Indications: Indicated for the treatment of proliferating infantile
hemangioma requiring systemic therapy. Initiate treatment at age 5 weeks to 5 months.
Safety and effectiveness for infantile hemangioma have not been established in pediatric
patients older than 1 year [4].
Administration
Intravenous: Administer 1 mg/mL at a rate not to exceed 1 mg per minute [14]. Consider
diluting to 0.1 mg/mL.
Oral: Administer during or right after a feeding, skip the dose if the child is not eating or is
vomiting [4]..
MEDICATION SAFETY
Contraindicated in patients with cardiogenic shock, decompensated heart failure, sinus

bradycardia, sick sinus syndrome, greater than first degree block (unless permanent
pacemaker is present), reactive airway disease, or diminished myocardial contractility [23]
[14][21][22].
When treating infantile hemangioma, Hemangeol™ is contraindicated in premature infants
with corrected age younger than 5 weeks, infants weighing less than 2 kg, asthma or history
653
of bronchospasm, heart rate less than 80 bpm, greater than first degree heart block,
decompensated heart failure, blood pressure less than 50/30 mmHg, or pheochromocytoma
[4].
Precautions
Cardiac ischemia may occur with abrupt discontinuation of therapy, gradually taper dose over
1 to 2 weeks and monitor the patient. Beta-blocker therapy may mask tachycardia occurring
with hypoglycemia and signs of hyperthyroidism [23]. Concomitant corticosteroids increase
the risk of hypoglycemia [4]. Treatment with epinephrine for severe anaphylactic reactions
may be less effective in beta-blocker-treated patients; consider alternative medications [23].
Propranolol may precipitate more severe heart failure. The risk of stroke increases in PHACE
(posterior fossa, hemangioma, arterial lesions, cardiac abnormalities/aortic coarctation, and
eye abnormalities) syndrome patients with severe cerebrovascular anomalies due to the
blood pressure reduction [4].
Adverse Effects
Adverse effects are related to beta-receptor blockade. Significant reductions in myocardial

function and hypotension resulting in cardiac compromise have been reported in association
with beta-blockers, especially during IV administration in infants. May cause AV block.
Bradycardia, fatigue, headache, dizziness, somnolence, diarrhea, anorexia, insomnia,
personality changes, and depression are the most common adverse effects reported in
children. Bronchospasm may occur. Case reports of hypoglycemia occurring in children after
therapeutic doses, in absence of diabetes [14][21][22][24][25][26].
Infantile hemangioma: The most common (10% or more) adverse events in infants
treated for infantile hemangioma were sleep disorders, aggravated respiratory tract
infections, peripheral coldness, agitation, diarrhea, somnolence, nightmare, irritability,
decreased appetite, abdominal pain, and vomiting [4].
Asymptomatic and symptomatic hypoglycemia, requiring hospitalization, have been reported
in infants receiving propranolol for the treatment of infantile hemangioma. Infants less than 3
months of age are at increased risk [27][28][12]. Hypoglycemia including hypoglycemic
seizures were typically associated with poor oral intake or concomitant infection [29].
Concomitant corticosteroids increase the risk of hypoglycemia [4].
Within 2 hours the effect on heart rate and blood pressure were evident [29].
Black Box Warning
Following abrupt cessation of therapy with beta-blockers, exacerbations of angina pectoris

and myocardial infarction have occurred. Warn against interruption or discontinuation of
therapy without physician advice [23].
D5W and NS.
654
Alteplase, dobutamine, heparin, hydrocortisone succinate, linezolid, milrinone, morphine,

potassium chloride, and propofol.
Monitoring
Continuous ECG monitoring should be done during acute treatment of arrhythmias and
during IV therapy. Measure systemic blood pressure frequently. Monitor vital signs and
measure blood glucose during initiation of treatment and after dosage changes. Assess for
increased airway resistance [4][12][14][21][22].
When treating infantile hemangiomas, monitor heart rate and blood pressure for 2 hours
after the first or increasing dose [4]. Perform a complete history and physical examination
with particular attention to cardiac and pulmonary systems. Electrocardiography may be
considered, particularly in younger infants, those with a low heart rate, and those at risk of
congenital heart disease (by examination or family history) [5]. Before treating large facial
infantile hemangioma with propranolol, assess for potential arteriopathy associated with
PHACE syndrome [4].
Pharmacology
Mechanism of action: Potential molecular mechanisms of action for propranolol in the

treatment of infantile hemangioma include vasoconstriction (reduction of blood flow to the
hemangioma), inhibition of angiogenesis (decreased expression of vascular endothelial
growth factor and inhibition of tubulogenesis of endothelial cells), and induction of apoptosis
in endothelial cells [30].
Propranolol is the most widely used nonselective β-adrenergic-receptor blocking agent. Peak
serum concentration is reached approximately 2 hours after an oral dose. Propranolol
undergoes significant first-pass hepatic metabolism, resulting in 30% to 40% bioavailability.
Protein binding is 70% in neonates. Serum half-life is prolonged in patients with liver disease.
Elimination is by renal excretion of metabolites.
ABOUT
Availability
Oral: 4 mg/mL and 8 mg/mL oral solution (contains 0.6% alcohol) and a 4.28 mg/mL
propranolol hydrochloride (3.75 mg/mL propranolol) alcohol-, paraben-, and sugar-free
solution (Hemangeol™); do not freeze. Do not shake Hemangeol™ before use and discard
655
the bottle 2 months after opening. Oral tablets available in 10-, 20-, 40-, 60-, and 80-mg
strengths.
Injectable: 1 mg/mL vials
Make a 0.1 mg/mL dilution by adding 1 vial (1 mg/mL) to 9 mL preservative-free normal
saline. Protect from light. Store at room temperature.
Extemporaneous Oral Compound

Propranolol 2 mg/mL and 5 mg/mL suspension are stable for 120 days when stored in amber
plastic bottles at 25°C or 4°C [31]
2 mg/mL
In a mortar, triturate 20 propranolol 40-mg tablets into a fine powder
Add Ora-Blend SF incrementally for a total of 400 mL
5 mg/mL
In a mortar, triturate 50 propranolol 40-mg tablets into a fine powder
Add Ora-Blend SF incrementally for a total volume of 400 mL
656
Protamine
Dose
Intravenous
Heparin-induced bleeding
Time since last heparin dose in minutes and protamine dose:
Less than 30 minutes: 1 mg per 100 units heparin received [1].
30 to 60 minutes: 0.5 to 0.75 mg per 100 units heparin received [1].
60 to 120 minutes: 0.375 to 0.5 mg per 100 units heparin received [1].
Greater than 120 minutes: 0.25 to 0.375 mg per 100 units heparin received [1].
Maximum dose: 50 mg
Low Molecular Weight Heparin-induced bleeding

Dalteparin: Protamine 1 mg IV for every 100 anti-Xa international units of dalteparin; if
APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of
protamine sulfate 0.5 mg per 100 anti-Xa international units of dalteparin may be
administered; maximum neutralization of the anti-Factor Xa activity is about 60% to 75%
[2].
Enoxaparin: Protamine 1 mg IV for every 1 mg of enoxaparin administered in the previous
8 hours; if more than 8 hours has elapsed since the last dose of enoxaparin was
administered, or if APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a
second infusion of protamine 0.5 mg per 1 mg of enoxaparin may be administered; if more
than 12 hours has elapsed since enoxaparin administration, protamine sulfate administration
may not be necessary; the maximum neutralization of the anti-Factor Xa activity is about
60% [3].
Tinzaparin: Protamine 1 mg IV for every 100 anti-Xa international units of tinzaparin; if
APTT (measured 2 to 4 hours after the first infusion) remains prolonged, a second infusion of
protamine 0.5 mg per 100 anti-Xa international units of tinzaparin may be administered; the
maximum neutralization of the anti-Factor Xa activity is about 60% [4].
Uses
For the treatment of heparin-induced bleeding [1][5].
For the treatment of low molecular weight heparin-induced bleeding. Although the
safety effectiveness of protamine sulfate among pediatric patients has not been approved by
the US Food and Drug Administration, the American College of Chest Physicians (AACP)
Evidence Based Clinical Practice Guidelines state that for treatment of low molecular weight
heparin (LMWH)-induced bleeding, protamine sulfate will neutralize anti-IIa activity and
partially neutralize anti-Xa activity. Protamine sulfate dosing is dependent on the dose of the
LMWH administered and repeated doses may be required [1].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/9F31B3/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
657
Administration
Administer intravenously. Recommended to be given undiluted, but if necessary, may further

dilute in D5W or NS. Infusion rate of a 10 mg/mL solution (undiluted) should not exceed 5
mg/min [1][5].
MEDICATION SAFETY
Adverse Effects
Excessive doses can cause serious bleeding problems. Hypotension, bradycardia, dyspnea,
and transitory flushing have been reported in adults [5].
Black Box Warning
Hypotension, cardiovascular collapse, pulmonary edema, pulmonary vasoconstriction, and

pulmonary hypertension may occur [5][6]. Cases of life-threatening pulmonary hypertension
and severe hemorrhagic pulmonary edema have been reported in infants after protamine
administration [7]. Risk factors for severe protamine adverse reactions include high doses,
rapid administration, repeated doses, previous exposure to protamine or protamine-
containing drugs (eg, NPH insulin, protamine zinc insulin, and certain beta blockers), known
hypersensitivity reactions to fish, severe left ventricular dysfunction, and abnormal
preoperative pulmonary hemodynamics. Vasopressors and resuscitation equipment should be
available. Should not be used for bleeding occurring without prior heparin use [5].
D5W and NS.
Cimetidine and ranitidine.
Most cephalosporins and penicillins.
Monitoring
658
Monitor vital signs, clotting functions, and blood pressure continuously. Observe for bleeding.
Pharmacology
Anticoagulant when given alone. Combines ionically with heparin to form a stable complex
devoid of anticoagulant activity. Rapid action after IV use (5 minutes) [5].
ABOUT
Available as a 10-mg/mL concentration (preservative-free) in 5- and 25-mL vials. Store at

room temperature Can be diluted in D5W or NS if necessary [5].
659
Protein C Concentrate (Human)
Dose
Prevention and Treatment of Venous Thrombosis and Purpura Fulminans

associated with Protein C Deficiency:
Acute Episode/Short-Term Prophylaxis:
Initial dose: 100 to 120 international units/kg IV, followed by 60 to 80 international
units/kg IV every 6 hours for next 3 doses [1].
Maintenance dose: 45 to 60 international units/kg IV every 6 or 12 hours [1].
Dose regimen should be adjusted to maintain a target peak protein C activity of 100%. After
resolution of acute episode, maintain trough protein C activity level above 25% for duration
of treatment. Continue treatment until desired anticoagulation is achieved [1].
Long-Term Prophylaxis: 45 to 60 international units/kg IV every 12 hours. Maintain

trough protein C activity level above 25% [1].
Uses
Treatment of patients with severe congenital protein C deficiency for the prevention and
treatment of venous thrombosis and purpura fulminans. Also indicated as a replacement
therapy [1][2][3][4].
For patients beginning warfarin therapy (vitamin K antagonist therapy), continue protein C
until stable anticoagulation is achieved. Begin warfarin therapy at a low dose and titrate up
to desired anticoagulation.
Administration
Administer solution at a concentration of 100 international units/mL by IV infusion at a

maximum rate of 0.2 mL/kg/minute[1].
MEDICATION SAFETY
Adverse Effects
Patients receiving protein C and initiating oral anticoagulant therapy are at increased risk for
warfarin-induced skin necrosis. Most serious and common adverse events reported were
hypersensitivity or allergic reactions and lightheadedness. Made from human blood. Bleeding
episodes were reported in clinical studies. Product contains small amount of heparin. Patients
660
with renal impairment may experience sodium overload (contains greater than 200 mg of
sodium in maximum daily dose) [1].
Monitoring
Measure plasma level of protein C before and during treatment. During acute thrombotic
events, measure protein C activity immediately before the next dose until the patient is
stabilized; dose regimen should be adjusted to maintain a target peak protein C activity of
100% (1 international unit/mL). After stabilization, maintain trough protein C activity level
above 25% (0.25 international units/mL). Monitor coagulation parameters (including platelet
count) during therapy. Closely monitor patients with renal impairment for sodium overload
(contains greater than 200 mg of sodium in maximum daily dose) [1][3].
Pharmacology
Protein C, a precursor of a vitamin K-dependent anticoagulant glycoprotein, is activated by

the thrombin/thrombomodulin-complex on the endothelial cell surface resulting in
subsequent potent anticoagulant effects. Once activated, protein C inactivates the activated
forms of factors V and VIII with subsequent reduction in thrombin formation. Other effects
include profibrinolytic effects. The pharmacokinetic profile in children has not been studied
extensively. One pharmacokinetic analysis determined a half-life of 4.2 to 8.3 hours and a
recovery of about 44% after infusion in children. Limited data also suggests a faster
clearance and larger volume of distribution in young children which may lead to significantly
reduced Cmax and therefore, reduced systemic exposure compared to older subjects [1][3].
ABOUT
Available in single-dose vials that contain nominally 500 (blue color bar) or 1000 (green color
bar) international units human protein C. Vials should be brought to room temperature and
reconstituted with 5 mL and 10 mL of sterile water for injection, respectively, to provide a
concentration of 100 international units/mL. Should be used within 3 hours of reconstitution.
A filter needle should be used to withdraw dose from vial. When reconstituted, contains the
following excipients: human albumin 8 mg/mL, trisodium citrate dihydrate 4.4 mg/mL, and
sodium chloride 8.8 mg/mL. Store unopened vials at 2 to 8 degrees C and protect
from light. Avoid freezing[1].
661
Pyridoxine
Dose
Pyridoxine-Dependent Seizures
Initial diagnostic dose: 50 to 100 mg IV push, or IM [1][2][3].
Maintenance dose: 50 to 100 mg orally every 24 hours [3]. High doses may be required
during periods of intercurrent illness.
Uses
Diagnosis and treatment of pyridoxine-dependent seizures. The test dose of pyridoxine to

confirm diagnosis of PDS is not well established. The consensus is that diagnosis of PDS is
confirmed when high doses of pyridoxine achieve complete seizure control that has been
resistant to traditional antiepileptics. Pyridoxine and antiepileptics are then withdrawn,
followed by a reoccurrence of clinical seizures that are, again, successfully treated with
pyridoxine monotherapy [4][5][1][2][3].
MEDICATION SAFETY
Adverse Effects
There have been reports of prolonged depression of neurologic and respiratory function, as
well as depression of cerebral electrical activity when given either orally or IV.
Cardiorespiratory monitoring is recommended and ventilator support may be necessary with
initial administration of pyridoxine. When given IV, there have been reports of bradycardia,
apnea, and hypotension. Pyridoxine injection contains aluminum that may be toxic with
prolonged IV administration in patients with renal impairment or in premature infants
(immature kidney function) [6][8][3].
Alkaline solutions
https://www.micromedexsolutions.com/micromedex2/librarian/CS/10C4A8/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
662
Iron salts and oxidizing agents. No data are currently available on heparin and potassium
chloride.
Monitoring
When possible, initial administration of pyridoxine should be accompanied by EEG

monitoring. Monitor for cardiorespiratory depression [6][5][1]. Monitor for signs of peripheral
neuropathy with long-term use [3]. A pyridoxine level than less 20 nanomoles/L is indicative
of deficiency [7]
Pharmacology
Pyridoxine is a coenzyme in amino acid and carbohydrate metabolism required for the
conversion of tryptophan to both niacin and neurotransmitter serotonin and conversion of
dopa to dopamine. It is also required for the synthesis of the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA). Pyridoxine-dependent seizures are a result of defective
binding of pyridoxine in the formation of GABA. They typically present in the neonatal period
or early infancy; however, seizures can occur for the first time at up to 3 years of age. In
addition to seizures, presentation may include hypothermia, jitteriness, encephalopathy,
abdominal distension, and vomiting. Administration of pharmacologic doses of pyridoxine will
correct this GABA deficiency [7][6][1][9].
ABOUT
Injection: 100 mg/mL (1 mL in 2-mL vial) [8]
Oral: 40 mg/mL oral liquid [10]. Tablets and capsules available in various strengths (25, 50,
100, 200, 250, and 500 mg).
Pyridoxine 1 mg/mL oral solution[11]
Using a syringe, draw up 1 mL (100 mg) from Pyridoxine 100 mg/mL vial for injection
Add to prescription bottle
Add 99 mL of syrup USP/NF (simple syrup)
Label with "Refrigerate" and an expiration of 30 days
Pyridoxine 25 mg/mL oral suspension[12]

Dilute pyridoxine hydrochloride 100 mg/mL for injection in Oral Mix or Oral Mix SF
663
Stable for 91 days in amber glass bottles, plastic bottles, or oral plastic syringes at 25°C
Stable for 91 days in amber glass or plastic bottles at 4°C
Pyridoxine 50 mg/mL oral suspension [13]

Pyridoxine, as an active pharmaceutical ingredient, was compounded with SyrSpend®
SF PH4 to make a 50 mg/mL suspension
Stable for 90 days at refrigeration (2 to 8 degrees C) and room temperature (20 to 25
degrees C)
Shake suspension for 1 minute before measuring dose
664
Quinupristin/Dalfopristin
Dose
7.5 mg/kg/dose every 12 hours by IV infusion.

Administration via a central catheter is recommended.
Uses
Limited to treatment of infections caused by gram positive organisms resistant to other

antibiotics, eg, methicillin-resistant Staph aureus
and vancomycin-resistant Enterococcus
faecium (not E faecalis
).
Administration
Give by intermittent IV infusion over 60 minutes at a concentration of 2 mg/mL. A

concentration up to 5 mg/mL may be used for central lines. Concentrations less than 1
mg/mL may be used if venous irritation occurs following peripheral administration. Flush
peripheral line with D5W before infusion if other drugs are administered through the same IV
line, and after infusion to minimize venous irritation. Infusion through a central line will
decrease the risk for venous irritation. Do not flush with saline or heparin due to
incompatibility [1].
MEDICATION SAFETY
Adverse Effects
Myalgias and arthralgias occur frequently in adults with hepatic or renal failure. Elevations in
serum bilirubin and transaminases are common. Diarrhea and rash occur infrequently.
D5W.
665
NS.
Aztreonam, fluconazole, metoclopramide, and potassium chloride.
Monitoring
Periodic measurement of serum bilirubin and transaminases. Assess peripheral IV site for
signs of inflammation.
Pharmacology
No data are available for infants. Synercid® is a parenteral antimicrobial agent which consists
of two streptogramin antibiotics (quinupristin and dalfopristin in a 30:70 ratio) that inhibit
bacterial protein synthesis by binding to separate sites on the bacterial ribosome. Serum half-
life of quinupristin in adults ranges from 1 to 3 hours, and of dalfopristin ranges from 5 to 9
hours. Seventy-five percent is excreted via the biliary route.
ABOUT
Synercid® is supplied as a lyophilized powder in single-dose, 10-mL vials containing 500 mg

or 600 mg. Store refrigerated. Reconstitute 500-mg and 600-mg vials by adding 5 mL or 6
mL of Sterile Water for Injection or D5W, respectively, resulting in a concentration of 100
mg/mL. Reconstituted solution should be diluted within 30 minutes. Before administration,
dilute with D5W to a concentration of 2 mg/mL. A concentration up to 5 mg/mL may be used
for central lines. Concentrations less than 1 mg/mL may be used if venous irritation occurs
following peripheral administration. Diluted solution is stable for 5 hours at room
temperature, or 54 hours if stored under refrigeration. Do not freeze.
666
Ranibizumab
Dose
Retinopathy of Prematurity, Type I

Intravitreal Route: Studies used intravitreal doses of 0.25 mg/0.025 mL [1][2][3] or 0.3
mg/0.03 mL [4]. Lower intravitreal doses, 0.12 mg/0.02 mL [5] and 0.2 mg/0.02 mL were
effective in a pilot study (n=19 infants) [5] and retrospective case series (n=21 infants) [5]
[6].
Premedication/Postprocedure medication
Anesthesia and broad-spectrum microbicide should be given prior to injection [7].
In infants, eyes were prepared with a topical anesthesia (0.5% proparacaine or 0.5%
tetracaine) and ophthalmic antiseptic (5% [2][1][8] or 10% [9] povidone iodine) . After the
procedure ophthalmic antibiotic drops were administered for 7 days [4][8].
Uses
Retinopathy of Prematurity (ROP)

Summary: In infants with Type 1 retinopathy of prematurity, one intravitreal ranibizumab
injection typically results in initial regression in all treated eyes [4][1][2]. In a prospective
randomized trial, recurrence occurred significantly more often with ranibizumab than with
laser photocoagulation (LPC) therapy in patients with Zone II, Stages 2 or 3 ROP with plus
disease [4]. A large retrospective case series reported a higher rate of recurrence with
ranibizumab compared with bevacizumab or LPC but treatment groups differed significantly
in relation to baseline characteristics [1]. Vascular abnormalities may persist after primary
treatment with ranibizumab [10]. Systemic vascular endothelial growth factor suppression
was not sustained with intravitreal doses of 0.12 mg or 0.2 mg in 19 infants [5]. Intravitreal
ranibizumab is well tolerated [4][1][2] but long-term systemic effects are unknown for
ranibizumab [4][1] and other vascular endothelial growth factor inhibitors [11].
Dose: Ranibizumab intravitreal doses of 0.12 mg/0.02 mL and 0.2 mg/0.02 mL were
effective without suppressing plasma vascular endothelial growth factor levels, in a
prospective randomized study (n=19 infants). The majority of eyes had posterior zone II,
stage 3 with plus disease. The second most common was zone I, stage 3 with plus disease.
At 24 weeks, rescue treatment was not needed in 17 of 18 treated eyes (94.4%) with 0.12
mg and 13 of 14 eyes (92.9%) with 0.2 mg. Recurrences severe enough to require
retreatment occurred in 2 infants in each group (8 eyes (21.1%)) [5].
•At 44 to 150 weeks postmenstrual age, fluorescein angiograms demonstrated 50% of eyes
reached vascularization to zone III, 40% had persistent vascular leakage, and 90% or more
showed vascular blunting, vascular dilatation, and/or capillary dropout with intravitreal
ranibizumab 0.15 to 0.2 mg for type 1 ROP including aggressive posterior ROP. At an
average of 85 weeks postmenstrual age, 15 of the 16 infants required bilateral laser ablation
for delayed vascularization in a retrospective study [10].
•In a prospective, randomized, single center study of 50 Han Chinese infants (100 eyes) with
667
Zone II retinopathy of prematurity (ROP) requiring treatment (ie, Stages 2 or 3 with plus
disease), significantly more eyes (52%) developed recurrence after a single dose of
intravitreal ranibizumab 0.3 mg compared with laser photocoagulation (LPC) therapy (4%).
Recurrence was defined as recurrent plus disease, neovascularization, or reformation of
ridge. Initial regression of neovascularization and plus disease occurred within 1 week in all
patients who received ranibizumab. All patients who recurred following ranibizumab achieved
successful regression following subsequent LPC therapy that was administered at a median of
12.62 weeks later. The one patient (4%) who failed initial LPC subsequently received one
injection of ranibizumab, resulting in successful regression. Mean follow-up time was
approximately 1 year and long-term systemic safety of ranibizumab was not evaluated [4].
•In a retrospective case series conducted at two Turkish centers of 134 infants (264 eyes),
recurrence to Stage 1 or 2 ROP occurred in 50% of the 22 infants treated with intravitreal
ranibizumab 0.25 mg, 5.5% of the 55 infants treated with intravitreal bevacizumab 0.625 mg
(significant difference compared with ranibizumab), and 1.8% of the 57 infants treated with
LPC therapy. Patients were treated according to the indications defined by the Early
Treatment for ROP (ETROP) study. At baseline, there were significant differences between
groups in postmenstrual age (PMA) at treatment (35.59, 34.75, and 36.03 weeks in the
ranibizumab, bevacizumab, and LPC groups, respectively) and the number of patients with
Zone II involvement (36.4%, 61.8%, and 87.7%, respectively). In addition, aggressive
posterior ROP (APROP) was present at baseline in 40,1%, 27.2%, and 1.8%, respectively.
After initial treatment, regression occurred in all patients. Of the 11 patients who had a
recurrence after initial ranibizumab, 8 spontaneously regressed, one received subsequent
LPC, and two received a second dose of ranibizumab (mean time to retreatment, 8.75
weeks). Of the 3 patients with recurrence after initial bevacizumab, one received subsequent
LPC, and two received a second dose of bevacizumab (mean time to retreatment, 14 weeks).
The final resolution rate was 100% in the ranibizumab and bevacizumab groups and 98.2%
in the LPC group (Stage 4A retinal detachment in one patient). Minor cases of transient
subconjunctival hemorrhage occurred in the drug treatment groups but no major ocular
complications were reported. Significantly higher rates of myopia (100%) and high myopia
(71.4%) in Zone I occurred in the LPC group compared with the ranibizumab (42.9% and
14.3%) and bevacizumab (57.1% and 23.8%) groups but rates for Zone II did not differ
significantly between groups. At an adjusted 1.5 years of age, the rate of emmetropia was
significantly higher in the ranibizumab (45.5%) and bevacizumab (50.9%) groups compared
with the LPC group (16.3%). Long-term systemic safety was not assessed [1].
•A retrospective single center study of 128 infants with Type 1 ROP and 18-month follow-up
examinations found recurrence rates of 16.7% (1 of 6 patients) with intravitreal ranibizumab
0.25 mg and 8.3% (1 of 12 patients) with intravitreal bevacizumab 0.625 mg following initial
regression within 48 hours in all patients who received either ranibizumab or bevacizumab.
Recurrence was defined as recurrent plus or preplus disease or neovascularization, or
progression of traction. In a third group of 36 patients who received LPC therapy, initial
regression occurred in 1 to 2 weeks except in 5 patients who required retreatment with LPC
at 10 days. Differences in the ranibizumab, bevacizumab, and LPC groups at baseline were
found in birth weight (840, 841, and 1112 grams, respectively), number of patients with
Stage 3 disease (16.7%, 16.7%, and 61.1%, respectively), APROP (83.3%, 83.3%, and
19.4%, respectively), and Zone II disease (66.7%, 83.3%, and 88.9%, respectively). A
fourth group of 74 patients with spontaneously regressed ROP was included. The two
patients with recurrence after ranibizumab or bevacizumab therapy achieved successful
regression following subsequent LPC therapy. Mean total vascularization time was
significantly shorter with ranibizumab (61.8 weeks of PMA) compared with bevacizumab (73
weeks of PMA). Following LPC, one patient experienced exudative retinal detachment and
nystagmus in both eyes and one patient had macular ectopia and nystagmus; no ocular
complications were noted in other groups other than transient preretinal hemorrhages [2].
668
Safety and effectiveness have not been established in pediatric patients [7].
Administration
Preparation
Syringe
•Only open the sealed tray under aseptic conditions [7].
•Snap off the syringe cap without turning or twisting [7].
•Remove any air bubbles [7]
Vial
•Under aseptic conditions, withdraw all of the ranibizumab vial contents (0.2 mL) through a
19-gauge x 1.5- inch, 5-micron filter needle attached to a 1-mL Luer lock syringe [7].
•After withdrawal, discard the filter needle [7]
•Do not use the filter needle for intravitreal injection [7]
•Remove any air bubbles [7]
Administration
•In pediatric patients a sterile 30-gauge [2][4][7], 31-gauge [1], or 32-gauge [9] 4-mm
needle injected ranibizumab 0.75 mm [10][9] to 1 mm [9] or 1.5 mm [10][2][4][1] posterior
to the temporal limbus into the vitreous cavity [10][9].
•To treat the contralateral eye, use a new vial or prefilled syringe and change the sterile
field, gloves, drapes, eyelid speculum, filter needle (vial only), and injection needles before
administration [7].
MEDICATION SAFETY
Contraindications
•Ocular or periocular infections [7].
Precautions
Cardiovascular: Arterial thromboembolic events (nonfatal stroke, nonfatal myocardial
infarction, or vascular death) have occurred [7].
Ophthalmic: Endophthalmitis and retinal detachments have been reported; monitor [7].
Ophthalmic: Intraocular pressure increase has been observed prior to injection and within
60 minutes after injection; monitor [7].
Adverse Effects
Ophthalmic Effects
The most commonly reported adverse effects in adult patients were conjunctival
hemorrhage, eye pain, vitreous floaters, and increased intraocular pressure [7].
Adverse events suspected to be related to intravitreal ranibizumab were conjuctival
669
hemorrhage, retinal detachment, injection site hemorrhage with the 0.12 mg dose (5 out of
10 infants) and conjunctival hemorrhage, corneal edema, retinal hemorrhage, and retinal
vascular disorder with the 0.2 mg dose (4 out of 9 infants). Serious retinal detachment was
suspected of to be related to intravitreal ranibizumab 0.12 mg (1 out of 10 infants) [5].
A large avascular area in zone II and zone III were present in 8 eyes (3%) at 24 weeks after
intravitreal ranibizumab . These eyes had abnormal vessel shunting and branching on fundus
photography [12].
More high myopia was seen in eyes treated with bevacizumab (14.6%) than those treated
with ranibizumab (0%) at 1 year of age in a retrospective study (n=37 infants) [3].
Cataract (0.7%) and vitreous and preretinal hemorrhage in 1 eye (0.4%) occurred in a
retrospective case series of 145 premature infants of retinopathy of prematurity [12].
Non-ophthalmic Effects
Respiratory failure and hypotension occurred in 1 infant with ROP administered intravitreal
ranibizumab 0.2 mg (1 out of 9 infants) [5].
Monitoring
•Monitor the treated eye for increased intraocular pressure with tonometry before and 30
minutes after intravitreal injection [7].
•Assess for perfusion of the optic nerve head immediately after intravitreal injection [7].
•Monitor the treated eye for signs and symptoms of endophthalmitis (redness, sensitivity to
light, pain, vision changes) following intravitreal injection [7].
Pharmacology
Mechanism of action
Ranibizumab is an inhibitor of the human vascular endothelial growth factor A (VEGF-A).
Ranibizumab binds to the receptor binding site of the active forms of VEGF-A, which prevents
VEGF-A from interacting with the surface receptors of endothelial cells. This blockage results
in reduced endothelial cell proliferation, vascular leakage, and new blood vessel formation
[7].
Cmax: Mean Cmax values of 1.7 +/- 1.1 ng/mL were observed in adults with neovascular
age-related macular degeneration following monthly intravitreal ranibizumab injections of 0.5
mg. The predicted serum ranibizumab concentrations in humans are approximately 90,000-
fold lower than vitreal concentrations [7].
Half-life: Average vitreous elimination half-life was approximately 9 days based on
population pharmacokinetic analysis of patients with neovascular age-related macular
degeneration following monthly intravitreal ranibizumab injections of 0.5 mg/eye [7].
ABOUT
670
Availability: 0.3 mg (6 mg/mL) or 0.5 mg (10 mg/mL) single-use, prefilled syringes and 0.3
(6 mg/mL) or 0.5 mg (10 mg/mL) 2-mL single use vials of ranibizumab [13].
Storage: Store vials and prefilled syringes under refrigeration and in original carton,
between 2 and 8 degrees C (36 and 46 degrees F). Protect prefilled syringes form light. Do
not freeze [13].
671
RaNITIdine
Dose
The marketing and distribution of all prescription and over-the-counter (OTC)

ranitidine drugs was discontinued in the US on 4/1/2020 due to the presence of
N-Nitrosodimethylamine (NDMA), which may result in exposure to unacceptable
levels of this impurity [1].
Oral: 2 mg/kg/dose orally every 8 hours [2][3].
IV
Term: 1.5 mg/kg/dose IV every 8 hours slow push [4].
Preterm:0.5 mg/kg/dose IV every 12 hours slow push [4].
Continuous IV infusion: 0.0625 mg/kg/hour IV maintained pH at or above 4; whereas,
0.031 mg/kg/hr maintained a median pH of 2.65 in 10 preterm neonates [5][6][7]; 0.03 to
0.06 mg/kg/hr was estimated to maintain an average raNITIdine concentration above 100
to 200 nanograms/mL in an exploratory, single-dose, pharmacokinetic study in 27 term
infants within the first day of life [8].
Extracorporeal membrane oxygenation (ECMO)

2 mg/kg/dose IV every 12 to 24 hours; gastric pH greater than 4 will be maintained for at
least 15 hours in neonates on ECMO based on limited data. A continuous infusion [9]
(initiated at 0.083 mg/kg/hr; increased in increments of 0.042 mg/kg/hr if gastric pH fell to
less than 4) maintained pH greater than 4 in more than 90% of 13 term neonates
undergoing ECMO [10].
Uses
or proton pump inhibitors should not be used for the treatment of crying and distress [13].
Prevention and treatment of stress ulcers and GI hemorrhage aggravated by gastric

acid secretion.
Apnea of prematurity: Reducing gastric acidity or increasing gastric motility for the sole
purpose to reduce apnea episodes is not supported by the literature [14].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/EB1EFE/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
672
Administration
IV bolus: May use 1 mg/mL preservative-free solution for injection or dilute in NS to a

maximum concentration of 2.5 mg/mL and give over at least 5 minutes (maximum 4
mL/minute)[11].
Intermittent IV infusion: Dilute in D5W or other compatible solution to a concentration of
no greater than 0.5 mg/mL and give over 15 to 20 minutes (maximum 5 to 7
mL/minute)[11]. A standard concentration of 1 mg/mL may be used [12].
Continuous IV infusion: Dilute in D5W or other compatible solution to a concentration of
0.5 mg/mL or less [11]. A standard concentration of 1 mg/mL may be used [12].
MEDICATION SAFETY
PRECAUTIONS
Hepatic: Use with caution in patients with hepatic dysfunction [16].
infections)
Special Populations: Avoid in patients with a history of acute porphyria as raNITIdine may
precipitate acute porphyric attacks [16].
Special Populations: In phenylketonuric patients, Zantac® 25 EFFERdose® tablets contain
phenylalanine 2.81 mg [16].
Adverse Effects
General: RaNITIdine is generally well tolerated by infants, children and adults, and has a
low incidence of adverse effects, including rash, headache, fatigue, irritability, dizziness,
nausea, constipation, and diarrhea, that are usually mild. Elevations in hepatic enzymes,
leukopenia, and bradycardia have been reported in adults [18][11].
Hematological: Severe thrombocytopenia (8 X 109/L) developed in a male infant

(gestational age 36 weeks and 5 days; weight 1.8 kg) 48 hours (5 days of age) after starting
ranitidine 0.5 mg/kg IV every 6 hours for prophylaxis of stress ulcer and as a potential gastric
emptying stimulator. Ranitidine was discontinued on day 6, platelets increased on day 8,
then normalized on day 12 [19].
673
Immunological
The use of H2-blockers in preterm infants has been associated with facilitating Candida
species colonization [20], and an increased risk for late-onset bacterial and fungal sepsis [21]
[20].
In a prospective, multicenter, observational study comparing VLBW neonates receiving
raNITIdine (n=91) to those not receiving raNITIdine (n=183), neonates receiving raNITIdine
had an increased rate of infection (37.4% versus 9.8%; OR 5.5; 95% CI, 2.9 to 10.4),
increased risk for NEC (9.8% versus 1.6%; OR 6.6; 95% CI, 1.7 to 25), and increased
mortality (9.9% versus 1.6%) [22].
In a retrospective, case-control study, H2-blocker use in VLBW infants was associated with
an increased incidence of NEC (OR 1.7; 95% CI, 1.34 to 2.19) [23].
D5W, D10W, and NS.
Acyclovir, acetazolamide, amikacin, aminophylline, ampicillin, atropine, aztreonam, cefazolin,

cefepime, cefoxitin, ceftazidime, chloramphenicol, clindamycin, dexamethasone, digoxin,
dobutamine, dopamine, enalaprilat, epinephrine, erythromycin lactobionate, fentanyl,
fluconazole, flumazenil, furosemide, gentamicin, glycopyrrolate, heparin, insulin,
isoproterenol, lidocaine, linezolid, lorazepam, meropenem, metoclopramide, midazolam,
milrinone, morphine, nicardipine, nitroprusside, pancuronium bromide, penicillin G,
piperacillin, piperacillin/tazobactam, potassium chloride, propofol, protamine, remifentanil,
tobramycin, vancomycin, vecuronium, vitamin K1, and zidovudine.
Amphotericin B, pentobarbital, and phenobarbital.
Monitoring
Gastric pH may be measured to assess efficacy.
Pharmacology
674
Mechanism of action: Inhibits gastric acid secretion by histamine H2-receptor antagonism
[9].
Tmax: Peak serum concentration occurs 1 to 3 hours after oral administration and is not
influenced by food.
Bioavailability is quite variable.
Metabolism: Hepatic biotransformation predominates after oral absorption, with 30%
excreted unchanged in the urine. In contrast, 70% of an IV dose is excreted unchanged in
the urine.
Half-life: Elimination half-life in neonates is 3 to 7 hours, and is prolonged in preterm
infants and patients with renal or hepatic insufficiency.
Pharmacokinetic Studies:
In children 1 day to 12.6 years of age (n=17), the half-life, Vd, and Cl were around 2.4
hours, 2 L/kg, and 11.7 mL/min/kg, respectively. In comparison in children older than 12
years of age (n=6), the half-life, Vd, and Cl were around 1.7 hours, 0.98 L/kg, and 9.89
mL/min/kg, respectively [9].
Extracorporeal membrane oxygenation: The half-life, Vd, and Cl were 6.6 hours, 1.8
L/kg, and 4.3 mL/min/kg, respectively, in 12 neonates on ECMO [9].
ABOUT
The marketing and distribution of all prescription and over-the-counter (OTC)

ranitidine drugs was discontinued in the US on 4/1/2020 due to the presence of
N-Nitrosodimethylamine (NDMA), which may result in exposure to unacceptable
levels of this impurity [1].
675
RifAMPin
Dose
Anthrax; meningitis or disseminated infection and meningitis cannot be ruled out

(as part of a triple therapy regimen) [1]
32 up to 38 weeks gestational age
Anthrax; meningitis ruled out (as part of a combination regimen) [1]

32 weeks or more gestational age: 10 mg/kg/dose IV every 24 hours
Haemophilus influenzae type b disease (invasive); prophylaxis for high-risk

contacts: 10 mg/kg per dose orally every 24 hours for 4 days.
Meningococcal disease (invasive); prophylaxis for high-risk contacts: 5 mg/kg per

dose orally every 12 hours for 2 days.
Staphylococcal infections, persistent

Oral: 10 to 20 mg/kg/dose every 24 hours. May administer with feedings.
IV: 5 to 10 mg/kg/dose every 12 hours [2][3][4][5], given via syringe pump.
Do not administer IM or subQ.
Uses
Anthrax[1]:

Plus
for neonates 37 weeks gestation or younger), or rifAMPin.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/CB8A07/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/6
676
ruled out) (IV)
Triple IV Therapy
moxifloxacin
Plus
(alternative).
Plus
Preferred: Linezolid. Alternatives in order of preference: clindamycin or rifAMPin or as
H influenzae type b; Prophylaxis
N meningitidis; Prophylaxis
Infective endocarditis The following recommendations are based on a consensus of
https://doi.org/10.1161/CIR.0000000000000298.
Initial Empirical Therapy or Culture-Negative Endocarditis*

Alternative
Unknown Organism First-Choice
Choice
Native valve (community acquired) Ampicillin/sulbactam
+ gentamicin
Vancomycin
"Late" prosthetic valve infection with or without vancomycin
+ gentamicin
(more than 1 year after surgery) For prosthetic valve involvement, add
rifAMPin
Nosocomial endocarditis associated with Vancomycin Unknown
vascular cannulae + gentamicin
(with or without rifAMPin if prosthetic
"Early" prosthetic valve endocarditis material present)
(1 year or less after surgery) + cefepime or cefTAZidime
* Culture-negative endocarditis (CNE): generally, attempt to culture the infecting organism for at
least 48 hours. Severely ill children need immediate treatment. Consider infectious disease
consultation for CNE
Baltimore, 2015

Streptococci
CefTRIAXone (for
677
course for aminoglycoside (AMG)-
enterococci) resistant enterococci or
CefTRIAXone +
gentamicin (not for
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)
Baltimore, 2015
Staphylococcal infections (persistent) in combination with vancomycin or

aminoglycosides [2][3][4][5].
Administration
Intravenous: Administer by intermittent IV infusion over 30 minutes to 3 hours at a

concentration not exceeding 6 mg/mL. Avoid extravasation during infusion [6].
678
MEDICATION SAFETY
Contraindications
Contraindicated in patients receiving ritonavir-boosted saquinavir; in patients receiving
atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir; and concomitant use with
praziquantel or within 4 weeks prior to praziquantel use (may restart rifampin 1 day after end
of praziquantel treatment) [8][9].
Precautions
Administration: Doses greater than 600 mg once or twice weekly; increased risk of serious
adverse effects, including shortness of breath, shock, anaphylaxis, and renal failure [8][9]
Administration: Rifadin® IV is for intravenous infusion only[9]
Concomitant use: Concomitant use of cefazolin and rifampin in patients at increased risk
for bleeding, avoid use; prolongation of prothrombin time may occur and lead to severe, life-
threatening or fatal, vitamin K-dependent coagulation disorder. If no other option available,
close monitoring required [10][11]
Concomitant use: Concomitant use with halothane should be avoided [8][9]
Dermatologic: Local irritation and inflammation due to extravascular infiltration has been
observed [9]
Endocrine and metabolic: Diabetes mellitus; diabetes management may be more difficult
[8][9]
Hematologic: Coagulation disorders that are vitamin K-dependent may occur; monitoring
recommended in patients at risk of vitamin K deficiency (eg, chronic liver disease, poor
nutritional status, on prolonged antibacterial drugs or anticoagulants) and consider
discontinuation if abnormal coagulation tests and/or bleeding occurs [10][11]
Hepatic: Hepatotoxicity of hepatocellular, cholestatic, and mixed patterns have been
reported with severity ranging from asymptomatic elevations in liver enzymes, isolated
jaundice/hyperbilirubinemia, symptomatic self-limited hepatitis to fulminant liver failure and
death. Severe hepatic dysfunction, including fatalities, have been reported in patients with
liver dysfunction and concomitant hepatotoxic agents; monitoring is recommended and
discontinuation may be necessary [12][13]
Immunologic: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome,
toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and Drug Reaction
with Eosinophilia and Systematic Symptoms (DRESS) syndrome, have been reported;
discontinue if symptoms or signs develop [8][9]
Immunologic: Systemic hypersensitivity reactions have been reported and may manifest as
fever, lymphadenopathy, or laboratory abnormalities (including eosinophilia, liver
abnormalities) with or without rash; monitoring recommended and discontinue therapy if
signs or symptoms occur [8][9]
Renal: Renal hypersensitivity reactions have been reported upon resuming therapy after
intentional or accidental interruption of daily regimen [8][9]
Adverse Effects
679
May cause yellow/orange/red/brown discoloration of sweat, urine, tears, sputum, or teeth
[14]. Extravasation may cause local irritation and inflammation. RifAMPin in a potent
inducer of several cytochrome P450 enzymes. If administered concomitantly, the following
drugs may have decreased pharmacologic effects due to increased metabolism:
aminophylline, amiodarone, cimetidine, corticosteroids, digoxin, enalapril, fluconazole,
midazolam, morphine, phenobarbital, phenytoin, propranolol, and zidovudine.
D5W and NS; both depend on concentration.
RifAMPin diluted to 8.33 mg/mL:

Vancomycin (40 mg/mL).
RifAMPin diluted to 6 mg/mL:
Amiodarone (12.5 mg/mL), amoxicillin/clavulanate (10/2 mg/mL), bumetanide (0.5 mg/mL),
midazolam (0.1 mg/mL), pantoprazole (8 mg/mL), and vancomycin (40 mg/mL).
Diltiazem and tramadol.
Monitoring
Monitor hepatic transaminases and bilirubin. Periodic CBC for thrombocytopenia. Observe IV
site for signs of extravasation.
Pharmacology
Mechanism of action: RifAMPin is a semisynthetic antibiotic with a wide spectrum of

antibacterial activity against staphylococci, most streptococci, , H influenzae Neisseria
species,
Legionella Listeria
, , some Bacteroides
species, Mycobacterium tuberculosis, and certain
atypical mycobacterium. Enterococci and aerobic gram-negative bacilli are generally
resistant. Not used as monotherapy because resistance may develop during therapy. Inhibits
transcription of DNA to RNA by binding to the beta subunit of bacterial RNA-polymerase [15].
Absorption: Well absorbed orally.
Metabolism: Rapidly deacetylated to desacetylrifampin (active metabolite) and undergoes
enterohepatic circulation.
680
Excretion: Nearly all of the rifAMPin excreted into the bile is deacetylated within 6 hours.
Half-life: Serum half-life ranges from 1 to 3 hours.
ABOUT
Injection
Availability: Lyophilized powder for injection in 600-mg vials.
Reconstitution: Reconstitute with 10 mL of sterile water for injection to make a final
concentration of 60 mg/mL. Reconstituted solution is stable for 24 hours at room
temperature.
Dilution: Further dilution is required; maximum concentration for infusion is 6 mg/mL.
Dilutions are stable at room temperature for 24 hours when prepared in normal saline and 4
hours when prepared in D5W [6].
Oral
Available in 150-mg and 300-mg capsules for oral use.
Extemporaneous compounding
RifAMPin 10 mg/mL oral suspension
A rifAMPin 10 mg/mL oral suspension can be prepared by using 4 rifAMPin 300-mg or 8
rifAMPin 150-mg capsules. The contents of the capsules should be crushed into a fine
powder, and a sufficient quantity of any one of four syrups (Syrup, NF, Simple syrup
(Humco™), fruit flavored syrup (Syrpalta®, Emerson), raspberry syrup (Humco™)) should be
added to bring the volume to 120 mL. This mixture should be labeled "shake well" and is
stable for 4 weeks at room or refrigerated temperature [6].
RifAMPin 25 mg/mL suspension
RifAMPin 25 mg/mL suspension is stable for 28 days when stored at room temperature or
refrigerated (microbial growth was not studied). To prepare 120 mL of rifAMPin 25 mg/mL
[16]:
Empty ten 300 mg capsules OR twenty 150 mg capsules into a mortar.
Add 20 mL of vehicle (choice of 1:1 Ora-Sweet/Ora-Plus, 1:1 Ora-Sweet SF/Ora-Plus,
OR cherry syrup) to the powder and mix until a uniform paste has formed.
Continue to add vehicle in geometric portions until almost to volume; mix thoroughly
after each addition.
Add the contents of the mortar to a prescription bottle; using vehicle, rinse mortar for
any leftover preparation and add to bottle.
Add sufficient amount of vehicle to a final volume of 120 mL.
Label bottle with "Shake Well Before Use" and "Protect from light".
681
Rocuronium
Dose
Time to maximum block for an intubating dose was shortest in infants (28 days up to 3
months) and longest in neonates (birth to younger than 28 days); duration of clinical
relaxation following an intubating dose is shortest in children (older than 2 years up to 11
years) and longest in infants[1].
Routine Tracheal Intubation: Initial, 0.6 mg/kg/dose IV; a lower dose of 0.45 mg/kg may
be used depending on anesthetic technique and patient age. Must be accompanied by
adequate anesthesia or sedation [1].
Routine Tracheal Intubation; Sevoflurane Induction: 0.45 mg/kg and 0.6 mg/kg IV
[1][2] produce excellent to good intubating conditions within 75 seconds [1].
Routine Tracheal Intubation; Halothane Induction: 0.6 mg/kg IV [1][3] produce
excellent to good intubating conditions within 60 seconds [1].
Skeletal Muscle Relaxation - Maintenance

General Anesthesia; Adjunct to Sevoflurane Induction/Isoflurane and Nitrous
Oxide
Bolus dosing: 0.15 mg/kg IV at reappearance of T3 [1].
Continuous infusion: 7 to 10 mcg/kg/minute IV at reappearance of T2 [1][4] with the
lowest dose requirement for neonates and the highest dose requirement for children older
than 2 years up to 11 years [1].
Uses
Rocuronium 0.45 mg/kg or 0.6 mg/kg IV under isoflurane anesthesia in newborns (N=20)
achieved good to excellent intubation conditions in most patients within 60 seconds in a
randomized study; a few patients experienced poor conditions with respect to position and
movement of vocal cords. Recovery of neuromuscular blockade for 0.45 mg/kg and 0.6
mg/kg, respectively, were 56.4 minutes and 100.8 minutes for T1 = 75% of baseline and
62.3 minutes and 94.8 minutes for train-of-four ratio of 0.7 [2].

Adjunct to general anesthesia to facilitate routine tracheal intubation, and to provide skeletal
muscle relaxation during surgery or mechanical ventilation [1].
Not recommended for rapid sequence intubation in pediatric patients [1]
Administration
•Must be accompanied by adequate analgesia and/or sedation [1].

•Administer IV push over 5 to 10 seconds. Available as a 10 mg/mL solution. May also give
as continuous IV infusion in compatible diluent at a concentration up to 5 mg/mL [1].
682
•Do not mix with alkaline solutions (eg, barbiturate solutions) in the same syringe or
administer simultaneously during IV infusion through the same needle [1].
MEDICATION SAFETY
Administration: Confirm proper selection of injected product and avoid confusion with
other injectable solutions in the critical care setting as administration results in paralysis,
which may lead to respiratory arrest and death; progression may be more likely in individuals
whom administration is unintended [1].
Administration: Must be accompanied by adequate anesthesia or sedation [1]
Administration: If extravasation occurs, immediately terminate the infusion and restart in
another vein [1]
Cardiovascular: An increased circulatory delayed time, which may occur with
cardiovascular disease, may delay onset time [1].
Cardiovascular: QT interval prolongation may occur with concomitant use of general
anesthetics in pediatric patients [1].
Concomitant use: Do not mix with alkaline solutions (eg, barbiturate solutions) in the same
syringe or administer simultaneously during IV infusion through the same needle [1].
Endocrine and metabolic: Malignant hyperthermia may occur [1].
Endocrine and metabolic: Acid-base or electrolyte abnormalities may potentiate or cause
resistance to neuromuscular blockade [1].
Immunologic: Severe, life-threatening, and fatal anaphylactic reactions have been
reported; caution advised in patients with previous anaphylactic reactions to other
neuromuscular blocking agents due to potential for cross-reactivity [1].
Musculoskeletal: Skeletal muscle weakness may occur while weaning from a ventilator
after chronic administration in the ICU; continuous monitoring recommended [5].
Musculoskeletal: Myopathy has been reported after long-term administration of other
nondepolarizing neuromuscular blocking agents in the ICU as monotherapy or when
combined with corticosteroids; when combined with a corticosteroid, limit period of use of
neuromuscular blocker and use in settings where benefits outweigh risks [1].
Musculoskeletal: Myasthenia gravis or myasthenic (Eaton-Lambert) syndrome; monitoring
recommended due to risk of profound neuromuscular blocking effects [5]
Neurologic: Residual paralysis after extubation may occur. Extubate only after sufficient
recovery from neuromuscular blockade [1].
Neurologic: Prolonged paralysis may occur while weaning from a ventilator after chronic
administration in the ICU; continuous monitoring recommended [1].
Neurologic: Potentiation of, or resistance to neuromuscular blockade may occur in cachectic
or debilitated patients, those with neuromuscular diseases, or carcinomatosis, or with
concomitant inhalation anesthetics (eg, enflurane, isoflurane), antibiotics, magnesium salts,
lithium, local anesthetics, procainamide, or quinidine; initial dosage adjustment may be
required [1].
Neurologic: Resistance to neuromuscular blocking agents can occur with an increased risk
in patients with burns, disuse atrophy, denervation, direct muscle trauma, cerebral palsy, or
chronic exposure to anticonvulsants (eg, carbamazepine, phenytoin) or nondepolarizing
agents; higher infusion rates may be required [1].
Respiratory: Increased pulmonary vascular resistance may occur; increased risk with
underlying pulmonary hypertension or valvular heart disease [1].
Tolerance: Tolerance may develop with chronic administration in the ICU; continuous
683
monitoring recommended [5].
Adverse Effects
The use of rocuronium in infants has only been studied in patients under halothane
anesthesia. The overall analysis of ECG data in pediatric patients indicates that the
concomitant use of rocuronium with general anesthetic agents can prolong the QTc interval.
Most pediatric patients anesthetized with halothane who did not receive atropine for
induction experienced a transient increase (30% or greater) in heart rate after intubation,
whereas only 1 of 19 infants anesthetized with halothane and fentanyl who received atropine
for induction experienced this magnitude of change. Aminoglycosides, vancomycin, and
hypermagnesemia may enhance neuromuscular blockade. Propofol has no effect. Phenytoin
may diminish neuromuscular blockade. Respiratory and metabolic acidosis prolong the
recovery time, respiratory alkalosis shortens it. Rocuronium may be associated with increased
pulmonary vascular resistance, so caution is appropriate in patients with pulmonary
hypertension. Extravasations cause local tissue irritation. The package insert statement that
rocuronium is not recommended for rapid sequence intubations in pediatric patients is due to
the lack of studies.
D5W, Lactated Ringer's, and NS.
Milrinone.
Micafungin.
Monitoring
Assess vital signs frequently and blood pressure continuously if possible.
684
Pharmacology
Rocuronium is an amino steroid nondepolarizing neuromuscular blocking agent that is an

analog of vecuronium with 10% to 15% of its potency. It has a rapid to intermediate onset
depending on dose and intermediate duration. It acts by competing for cholinergic receptors
at the motor end-plate. This action is antagonized by acetylcholinesterase inhibitors, such as
neostigmine and edrophonium. Plasma levels of rocuronium follow a three compartment
open model following intravenous administration. The rapid distribution half-life is 1 to 2
minutes and the slower distribution half-life is 14 to 18 minutes. Onset of clinical effect
usually occurs within 2 minutes and the duration ranges from 20 minutes to 2 hours. Larger
doses (0.9 to 1.2 mg/kg) lead to more rapid onset and longer duration of clinical effect. It
can have differential effects on various muscle groups (eg, laryngeal vs adductor pollicis vs
diaphragm). The onset of laryngeal adductor paralysis is significantly slower with rocuronium
compared with succinylcholine. Despite this difference, rocuronium has the fastest onset of
any currently available nondepolarizing muscle relaxant. Average half-life in newborns is 1.1
hours. Rocuronium is approximately 30% protein bound, and is primarily excreted by the
liver. There are no known metabolites.
ABOUT
Zemuron® for intravenous injection is available in 5 mL and 10 mL multiple-dose vials

containing 10 mg/mL. Each mL contains 10 mg rocuronium bromide and 2 mg sodium
acetate. The solution is clear, colorless to yellow/orange, and is adjusted to isotonicity with
sodium chloride and to a pH of 4 with acetic acid and/or sodium hydroxide.
Storage: Store refrigerated, 2 to 8 degrees C (36 to 46 degrees F). DO NOT FREEZE. Upon
removal from refrigeration to room temperature storage conditions (25 degrees C/77 degrees
F), use within 60 days. Use opened vials within 30 days.
To prepare a 1 mg/mL solution, dilute 1 mL of the 10 mg/mL solution up to a final volume of
10 mL with NS. Dilution stable for 24 hours. Do not mix with alkaline solutions[1].
685
Sildenafil
Dose
Persistent Pulmonary Hypertension, adjunct
Retinal vascularization must be established before sildenafil is used in extremely preterm

infants [1].
IV: loading dose of 0.4 mg/kg over 3 hours, followed by a continuous infusion of 1.6
mg/kg/day (0.067 mg/kg/hour). These data are based on a dose-escalation trial (n=36) and
not an efficacy trial [2].
Oral: 0.5 to 1 mg/kg/dose orally 3 times daily [1].

Pharmacokinetics of sildenafil in neonates are highly variable [3]. Careful dose titration while
monitoring oxygenation and blood pressure is required.
Uses
Persistent pulmonary hypertension (PPHN), adjunct: The Food and Drug

Administration recommends against the use, particularly chronic use, of sildenafil in children
due to an observation of increased mortality with increased doses in a long-term, pediatric,
clinical trial. However, there may be situations when benefit outweighs risk [5]. Adjunctive
sildenafil may be used in infants with PPHN who are refractory to inhaled nitric oxide,
particularly when the oxygenation index is greater than 25 [1].
Use limited to treatment of patients with PPHN refractory to inhaled nitric oxide (iNO) and
other conventional therapies, those who are persistently unable to be weaned off of inhaled
nitric oxide, or in situations where nitric oxide and high frequency ventilation are not
available. According to an intervention review of the use of sildenafil in neonates with PPHN,
sildenafil was associated with a significant reduction in mortality with a number need to treat
to benefit of 3. All studies included in the review were in resource-limited settings [6]. In a
prospective, randomized trial (n=65), oral sildenafil was more effective than magnesium
sulfate in a setting without iNO or high frequency ventilation based on time to adequate
effect, duration of mechanical ventilation, and use of inotropic support [7].
Sildenafil has been reported to improve pulmonary blood flow in patients with severe
Ebstein's anomaly [8].
A retrospective study (n=7) reported reductions in pulmonary hypertension, and improved
respiratory status and oxygenation in neonates with congenital diaphragmatic hernia (CDH)
with pulmonary hypertension refractory to inhaled nitric oxide [9].
Administration
686
Available as 0.8 mg/mL IV solution [4]. Infuse the loading dose over 3 hours [2].
MEDICATION SAFETY
Contraindicated in patients taking organic nitrates in any form and in patients with a
known hypersensitivity to sildenafil [10].
Precautions
Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported [11][10];
increased risk with crowded optic disc, hypertension, coronary artery disease, hyperlipidemia,
or smoking [11].
Bleeding events have been reported in postmarketing surveillance, though a causal
relationship has not been established. Hypersensitivity reactions, including rash and urticaria,
have occurred with sildenafil therapy [10]. An increased mortality with increased doses in a
long-term, pediatric, clinical trial has been observed [5].
Adverse Effects
Use in neonates should be restricted and considered experimental. Data in neonates remain
limited. The most concerning short-term adverse effects are worsening oxygenation and
systemic hypotension [2]. There is one case report of bleeding after circumcision in a
neonate receiving chronic therapy [12]. Use with caution in infants with sepsis. Sildenafil
causes transient impairment of color discrimination in adults, and there is concern that it
could increase the risk of severe retinopathy of prematurity if used in extremely premature
infants. In a study of neonates receiving sildenafil for at least weeks (n=22), positive ocular
findings were reported in 4 patients, none of which were considered drug-related [13].
Sildenafil did not increase the risk of retinopathy of prematurity (odds ratio 1.35 (95% CI,
0.39 to 4.62; p=0.63)) in a case-control study (n=68) of premature infants born before 30
weeks gestation. One infant each in the sildenafil group and control group required laser
treatment [14].
Monitoring
Continuous monitoring of blood pressure and oxygenation [2].
Pharmacology
687
Sildenafil is a selective phosphodiesterase type-5 (PDE5) inhibitor. This inhibition leads to
accumulation of cyclic GMP in pulmonary smooth muscle cells, causing pulmonary vascular
relaxation. It may also potentiate the effect of inhaled nitric oxide. Pharmacokinetics in
neonates receiving sildenafil, both intravenously and orally, are highly variable [15][3]. Oral
absorption is rapid in adults with approximately 40% bioavailability; peak concentrations are
reached in 30 to 120 minutes. Protein binding is 94%. It is metabolized primarily by hepatic
CYP3A4 to an active metabolite (N-desmethyl sildenafil) that also has PDE5 inhibitory activity
[16]. The terminal half-life of sildenafil in neonates on Day 1 of life is estimated to be 56
hours, and that of the metabolite 10 hours. This compares to adult data where both sildenafil
and the metabolite have terminal half-lives of 4 hours. Clearance increases rapidly (triples) in
the first week of life, likely related to both maturation and improvements in patient
hemodynamics. Patients with significant hepatic or renal dysfunction have reduced clearance.
Significant increases in sildenafil concentrations may occur when used concomitantly with
drugs that are CYP3A4 inhibitors: eg, fluconazole, erythromycin, amlodipine, and cimetidine
[16].
The pharmacokinetics of a single oral dose of 1.5 mg/kg sildenafil (dissolved in water)
administered to 12 children (1.5 to 15 years of age) with pulmonary arterial hypertension
were [17]:
Half-life 2.41 +/- 1.18 hours
Vd 20.1 +/- 14.5 L
Total clearance 5.85 +/- 2.81 L/hr
Tmax 0.92 +/- 0.3 hours
Cmax 366 +/- 179 ng/mL
AUC 2061 +/- 638 ngXhr/mL
ABOUT
Oral Revatio® is supplied as 20-mg tablets and an oral suspension [18]. Viagra® is supplied
as 25-mg, 50-mg, and 100-mg tablets.
Revatio® oral suspension must be constituted by the pharmacist prior to dispensing to the
patient. To prepare the oral solution, shake the Revatio® bottle to loosen the powder.
Remove the cap and add 60 mL of water. Shake the closed bottle for a minimum of 30
seconds. Open the bottle and add an additional 30 mL of water and shake the closed bottle
for another 30 seconds. The prepared solution contains sildenafil 10 mg/1 mL. Once
reconstituted, the oral solution should be stored below 30 degrees C (86 degrees F) or in the
refrigerator for up to 30 days. Do not freeze [18].
The Revatio® oral suspension is supplied as an off-white powder for constitution, forming a
white to off-white grape flavored solution, which when constituted with water as directed
contains 10 mg/mL of sildenafil. Available in glass bottles containing approximately 112 mL
of solution after constitution; a press-in bottle adaptor and oral syringe are supplied with
each bottle. The inactive ingredients of sildenafil oral solution include sorbitol, citric acid
anhydrous, sucralose, sodium citrate dihydrate, xanthan gum, titanium dioxide, sodium
benzoate, colloidal silicon dioxide anhydrous and grape flavor [18].
Intravenous Revatio® is supplied as a single-use vial containing 10 mg (12.5 mL) of
688
sildenafil, equivalent to 0.8 mg sildenafil per mL. Each mL of solution also contains 50.5 mg
dextrose and water for injection [16].
To prepare an oral 2.5-mg/mL suspension (150 mL), thoroughly crush fifteen (15) 25-mg
tablets into a fine powder and add a 1:1 mixture of Ora-Sweet® and Ora-Plus® or
methylcellulose 1% and Simple Syrup, NF to make a final concentration of 2.5 mg/mL.
Suspension is stable for 91 days in plastic bottles at 4 and 25 degrees C [19]. This
extemporaneous suspension was made using the Viagra® (sildenafil) dosage form.
689
Simethicone
Dose
Dosage should be weight-based whenever possible, otherwise age should be used for dosing
[1]
Gas relief
Oral route
Emulsion/Suspension
Younger than 2 years and less than 11 kg: 20 mg orally as needed, after meals and at
bedtime. MAX 240 mg/day[2][1]
Uses
Colic: Both placebo and simethicone improved colic symptoms, with no difference between
the 2 groups, in a double-blind, randomized, crossover study of 83 full term infants (2 to 8
weeks of age) [3].
Pediatric FDA Approved Indications: This drug has not been found by the US Food and
Drug Administration (FDA) to be safe and effective, and the drug product labeling has not
been approved by the FDA [1].
Administration
Oral route
Emulsion/Suspension
Shake well prior to use [2][1]
Administer with enclosed syringe only. Do not use dropper, spoon, or other dosing device [1]
Dispense into child's mouth toward inner cheek [2][1]
Dose can be mixed with 1 ounce of cool water, formula, or other suitable liquid [2][1]
ABOUT
Oral route
Emulsion/Suspension
Availability: 20 mg/0.3 mL emulsion or suspension/drops [1]
Storage: Store between 20 and 25 degrees C (68 and 77 degrees F). Do not freeze [2][1].
690
691
Sodium Bicarbonate
Dose
Metabolic acidosis
Dosage based on base deficit:
HCO3 needed (mEq) = HCO3 deficit (mEq/L) x (0.3 x body wt [kg])
Administer half of calculated dose, then assess need for remainder [1].
Resuscitation (routine use not recommended)

Usual dosage: 1 to 2 mEq/kg IV/IO slowly [2].
Uses
Metabolic acidosis: Treatment of normal anion gap metabolic acidosis caused by renal or
gastrointestinal losses.
Cardiac resuscitation: Sodium bicarbonate is not a recommended therapy in neonatal

resuscitation guidelines [5][2]. After effective ventilation is established in patients with
documented metabolic acidosis, sodium bicarbonate may be used [2].
Administration
Intravenous: Administer slow IV push. Rapid IV administration (10 mL/min) of hypertonic

sodium bicarbonate may lead to serious consequences (hypernatremia, a decrease in CSF
fluid pressure, and possible intracranial hemorrhage) in neonates and children younger than
2 years. MAX 8 mEq/kg/day[3]. The preferred concentration for slow IV administration in
neonates is the 4.2% strength (0.5 mEq/mL) [3][2]. Other recommended pediatric
concentrations for infusions are 0.25 mEq/mL and 1 mEq/mL [4].
Do not administer by the endotracheal route [2].
MEDICATION SAFETY
Adverse Effects
Bicarbonate administered during inadequate ventilation increases PCO2, thereby decreasing

pH. Rapid infusion of hypertonic solution is linked to intracranial hemorrhage in neonates and
infants. Extravasation may cause local tissue necrosis at IV site. Fluid overload,
hypocalcemia, hypokalemia, and hypernatremia may occur. Aggressive therapy may result in
https://www.micromedexsolutions.com/micromedex2/librarian/CS/0E5D4B/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
692
metabolic alkalosis (associated with muscle twitching, irritability, and tetany) [1][6][7].
D5W, D10W, and NS.
Acyclovir, amikacin, aminophylline, amphotericin B, atropine, aztreonam, cefepime, cefoxitin,

ceftazidime, ceftriaxone, chloramphenicol, cimetidine, clindamycin, dexamethasone,
erythromycin lactobionate, esmolol, famotidine, furosemide, heparin, hydrocortisone
succinate, ibuprofen lysine, indomethacin, insulin, lidocaine, linezolid, milrinone, morphine,
nafcillin, netilmicin, penicillin G, phenobarbital, piperacillin/tazobactam, potassium chloride,
propofol, remifentanil, vancomycin, and vitamin K1.
Amiodarone, ampicillin, calcium chloride, cefotaxime, dobutamine, dopamine, epinephrine,

glycopyrrolate, imipenem/cilastatin, isoproterenol, magnesium sulfate, meropenem,
methadone, metoclopramide, midazolam, nicardipine, norepinephrine, oxacillin, phenytoin,
and ticarcillin/clavulanate.
Monitoring
Monitor ABGs, acid/base status, and serum calcium and potassium [6].
Pharmacology
When bicarbonate is administered, buffering of hydrogen ions occurs, leading to increased

production of carbon dioxide and water. Animal studies of resuscitation demonstrate poor
coronary perfusion leads to carbon dioxide accumulation within the myocardium, leading to
decreased myocardial contractility.
ABOUT
693
Supplied by many manufacturers in multiple concentrations: 4% (0.48 mEq/mL), 4.2% (0.5

mEq/mL; 1 mOsmol/mL), 5% (0.6 mEq/mL; 1.19 mOsmol/mL), 7.5% (0.9 mEq/mL; 1.79
mOsmol/mL) and 8.4% (1 mEq/mL; 2 mOsmol/mL). Maximum concentration used in
neonates is 4.2% (0.5 mEq/mL). May dilute with sterile water for injection. Do not infuse
with calcium or phosphate containing solutions; precipitation will occur.
694
Sodium Chloride (Normal Saline)
Dose
Resuscitation (volume expansion): 10 mL/kg IV of sodium chloride 0.9% over 5 to 10

minutes. Consider a second dose of 10 mL/kg if there is no significant improvement after the
first dose. Normal saline (sodium chloride 0.9%) is the recommended volume expander.
Lactated Ringer's is an acceptable alternative [1].
Uses
Resuscitation: Volume expanders should be considered in neonates with clinically apparent

hypovolemia, but should not be used in the absence of evidence of acute blood loss. Normal
saline (sodium chloride 0.9%) is the preferred isotonic crystalloid solution, and Lactated
Ringer's is an acceptable alternative. In babies with severe fetal anemia, O Rh-negative
packed red blood cells should be considered as part of volume expansion [1]. The American
Heart Association (AHA) did not review the use of volume expanders in the 2015 Neonatal
Resuscitation guidelines; therefore, the 2011 AHA guideline still applies [2]
Administration
For resuscitation (volume expansion), give normal saline over 5 to 10 minutes. Consider a
longer duration of administration in preterm neonates less than 30 weeks GA [1].
MEDICATION SAFETY
Large fluid volumes can decrease cardiac output in hypoxic infants. Avoid rapid
administration of volume expanders due to the risk for intracranial hemorrhage. Rapid
administration of packed red blood cells may precipitate heart failure [1].
Monitoring
Monitor heart rate, blood pressure.
695
696
Sodium Glycerophosphate
Dose
Phosphate Supplement:1 to 1.5 mmol/kg/day, individualized to needs of patient [1].
Uses
Phosphate supplementation: After administration of sodium glycerophosphate 1.5

mmol/kg/day, mean increases in plasma phosphorus concentrations were 0.33+/-0.08
mmol/L at 12 hours, 0.72 +/-0.3 mmol/L at 36 hours, and 0.9+/-0.3 mmol/L at 60 hours (p
less than 0.0001 for all values) from a baseline of less than 0.5 mmol/L in a retrospective
report of very low birthweight neonates with hypophosphatemia receiving parenteral
nutrition (n=19; mean gestational age 28+/-3 weeks). All patients had been receiving
parenteral nutrition solutions with inorganic calcium and phosphorus salts at the limit of
solubility when hypophosphatemia resulted. The switch to sodium glycerophosphate as the
sole phosphorus source not only increased the amount of phosphorus that could be
administered each day, but also allowed an increase in the amount of calcium infused to 1.5
mmol/kg/day. By 60 hours, all patients had achieved a plasma phosphorus concentration of
1.5 mmol/L or greater [2].

Because of the critical shortage of phosphate injection in the United States market, an
alternative imported formulation of Glycophos™ has been made available; however, it is not
approved by the US Food and Drug Administration [3].
Administration
Must be diluted before administration. Administer over no less than 8 hours [1].
MEDICATION SAFETY
Contraindicated in patients with dehydration, hypernatremia, hyperphosphatemia, severe

renal insufficiency, or shock [1].
Product contains 2 mEq/mL of sodium. Use with caution in patients with renal impairment
[1].
Barcodes on the Glycophos™ product will not be recognized by scanning systems used in the
697
US and should not be used. The product should be manually input into the system. Alternate
procedures should be put in place to assure that the correct drug product is being prepared
and administered to the patient [3].
Adverse Effects
No adverse effects of sodium glycerophosphate have been reported [2][1].
Up to 10 mL of Glycophos™ and 10 mmol of calcium (as CaCl2) may be added to 1000 mL of

D5W [1].
D20W [1].
D50W [1].
As a reference only (these products are not available in the US), up to 120 mL of
Glycophos™ and 48 mmol of calcium (as CaCl2) may be added to the following amino acid
solutions (1000 mL) [1]:
Vamin 14 (Ca 5 mmol/L; pH 5.4 to 5.8; amino acids 8.5%; nitrogen 13.5 g/L)
Vamin 14 (pH 5.4 to 5.8, amino acids 8.5%; nitrogen 13.5 g/L) electrolyte free
Vamin 18 (pH 5.4 to 5.8; amino acids 11.4%; nitrogen 18 g/L) electrolyte free
Vaminolact (pH 5.2; amino acids 6.53%; nitrogen 9.3 g/L)
More complete information on the composition of these products is available [4][5].
Monitoring
Regularly monitor phosphate status [1].
Pharmacology
Sodium glycerophosphate is an organic phosphate, which is different from the inorganic

phosphate products usually used in the US[3]. Organic phosphates tend to be more
compatible with calcium, such that solutions of calcium and phosphate may exist at higher
concentrations without precipitation and, at higher pH (greater than 6), organic phosphate is
less likely to precipitate [3]. It is used as an IV nutritional supplement when plasma
phosphate concentrations are low. Bioavailability is dependant on hydrolysis of the phosphate
group from the glycerophosphate molecule, which occurs most efficiently at plasma
698
concentrations of greater than 0.7 mmol/L. Normal serum alkaline phosphatase is capable of
hydrolyzing approximately 12 to 15 mmol of sodium glycerophosphate each day.
Pharmacokinetic data not available for infants [1].
ABOUT
Glycophos™ (sodium glycerophosphate) is a preservative-free concentrated solution (pH 7.4)

containing 2 mEq/mL of sodium and 1 mmol/mL of phosphate in a 20-mL single-dose plastic
vial [3]. Do not store above 25 degrees C. Do not freeze. Discard vial after use [1].
Note: Glycophos™ contains 1 mmol/mL of organic phosphate. Sodium and potassium
phosphate products typically used in the US are 3 mmol/mL of inorganic phosphate [3].
699
Sodium Nitroprusside
Dose
Usual Dosage
Initial dosage: 0.3 mcg/kg/min as an IV infusion; titrate every few minutes until the
desired effect is achieved or [1] up to MAX 10 mcg/kg/min , but for no longer than 10
minutes at the maximum rate [2][3] or the shortest duration possible [1].
Heart failure: 0.3 to 4 mcg/kg/minute IV infusion MAX 6 mcg/kg/min [4].
Risk of thiocyanate toxicity with prolonged administration (more than 72 hours) [5].
Dose Adjustments
Renal
GFR less than 30 mL/min/1.73m2:: Limit mean infusion rate to less than 3 mcg/kg/min
[6]
Anuria: Limit the mean infusion rate to 1 mcg/kg/min [6]
Uses
•Acute treatment of hypertensive emergencies.

•Acute afterload reduction in patients with refractory congestive heart failure.
Pediatric FDA Approval: Indicated for immediate reduction of blood pressure in pediatric
patients in hypertensive crises. Indicated for induction and maintenance of controlled
hypotension in pediatric patients during surgery, to reduce bleeding [6].
Administration
Administer as a continuous IV infusion at a concentration of 50 to 500 mcg/mL (0.05 to 0.5

mg/mL). Use a large vein for IV. Protect infusion from light during administration (not
necessary to cover tubing) [6][7]. Some institutions use standard concentrations of 60, 125,
200, 400, 500, and 1000 mcg/mL [8]. Administer by volumetric infusion pump [6].
MEDICATION SAFETY
https://www.micromedexsolutions.com/micromedex2/librarian/CS/64C438/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/4
700
Contraindications
Acute heart failure associated with reduced peripheral vascular resistance [6][3]
Compensatory hypertension (aortic coarctation or arteriovenous shunting) [6][3]
Concomitant sildenafil, tadalafil, vardenafil, or riociguat [6]
Congenital (Leber) optic atrophy [6][3]
Inadequate cerebral circulation or moribund patients (ie, ASA class 5E) coming to emergency
surgery [6][3]
Tobacco amblyopia [6][3]
Precautions
Anesthesia: Patient's ability to compensate for anemia and hypovolemia may be
diminished; when possible, correct preexisting condition prior to use [6][3]
Hematologic: Methemoglobinemia may occur [6]
Hepatic: Hepatic dysfunction predisposes a patient to cyanide toxicity [6].
Neurologic: Increases in intracranial pressure can occur [6][3]
Thiocyanate toxicity: Can occur and may be life-threatening when levels reach 200 mg/L;
monitoring recommended and dose adjustment may be required, especially in patients with
renal impairment or anuria. Renal hemodialysis may be used to eliminate thiocyanate if
severe toxicity occurs [6]
Special populations: Exercise extreme caution in patients who are especially poor surgical
risks (eg, ASA Class 4 and 4E) [3]
Adverse Effects
Severe hypotension and tachycardia. Cyanide toxicity may occur with prolonged treatment
(greater than 3 days) and high (greater than 3 mcg/kg per minute) doses. Use with caution
in liver and renal failure patients due to possible impairment of the metabolism of cyanide to
thiocyanate. Extravasation can cause tissue sloughing and necrosis.
Black Box Warning
•Nitroprusside is not suitable for direct injection; the reconstituted solution must be further
diluted in sterile 5% dextrose injection before infusion [3](the Ready-To-Use solution (200 or
500 mcg/mL) may be used without further dilution).
•Nitroprusside can cause precipitous decreases in blood pressure, which may result in
irreversible ischemic injuries or death; monitor blood pressure continuously while patient is
on therapy [1].
• Except when used briefly or at low (less than 2 mcg/kg/min) infusion rates , sodium
nitroprusside gives rise to important quantities of cyanide ion, which can reach toxic,
potentially lethal levels. The usual dose rate is 0.5 to 10 mcg/kg/min, but infusion at the
maximum dose rate should never last more than 10 minutes. If blood pressure has not been
adequately controlled after 10 minutes of infusion at the maximum rate, administration of
sodium nitroprusside should be terminated immediately [3].
•Sodium nitroprusside metabolism produces dose-related cyanide, which can be lethal. A
patient’s ability to buffer cyanide will be exceeded in less than one hour at the maximum
dose rate (10 mcg/kg/min); limit infusions at the maximum rate to as short a duration as
possible [1].
701
•Although acid-bas e balance and venous oxygen concentration should be monitored and
may indicate cyanide toxicity, these laboratory tests provide imperfect guidance [3].
D5W, NS, and LR only.
Caffeine citrate, calcium chloride, cimetidine, dobutamine, dopamine, enalaprilat,

epinephrine, esmolol, famotidine, furosemide, heparin, indomethacin, insulin, isoproterenol,
lidocaine, magnesium, micafungin, midazolam, milrinone, morphine, nicardipine,
nitroglycerin, pancuronium, potassium chloride, procainamide, propofol, prostaglandin E1,
ranitidine, and vecuronium.
Amiodarone.
Monitoring
Continuous heart rate and intra-arterial blood pressure monitoring is mandatory. Daily
measurement of RBC cyanide (should be less than 200 ng/mL) and serum thiocyanate
(should be less than 50 mcg/mL) concentrations. Assess frequently for development of
metabolic acidosis. Daily assessment of renal and hepatic function. Monitor IV site closely.
Pharmacology
Direct-acting nonselective (arterial and venous) vasodilator. Immediately interacts with RBC
oxyhemoglobin, dissociating and forming methemoglobin with release of cyanide and nitric
oxide. Rapid onset of action with a serum half-life of 3 to 4 minutes in adults. Further
metabolized to thiocyanate in the liver and kidney. Thiocyanate is renally eliminated with a
half-life of 4 to 7 days.
ABOUT
702
Available: Powder for injection in 2-mL single-dose 50-mg vials, 50 mg/2 mL (25 mg/mL)
concentrated solution, and ready-to-use 10 mg/50 mL (200 mcg/mL) and 50 mg/100 mL
(500 mcg/mL) solution in NS.
Powder for injection: Reconstitute powder for injection with 2 to 3 mL of D5W or NS. Do
not administer reconstituted drug directly from vial. Dilute entire vial contents to a
final concentration of 50 to 1000 mcg/mL (0.05 to 1 mg/mL) in D5W or NS. Use within 24
hours of preparation. Protect from light with aluminum foil or other opaque material. Blue,
green or deep red discoloration indicates nitroprusside inactivation. Slight brownish
discoloration is common and not significant.
Ready-to-use (200 mcg/mL and 500 mcg/mL): Protect from light, should be stored in
its carton until used. Should be clear colorless to red/brown color. Do not use if solution is
blue, green, or bright red [1].
703
Sodium phenylacetate/Sodium benzoate
Dose
Pending Definitive Diagnosis of Urea Cycle Enzyme Deficiency:

Loading dose: Sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg in
combination with arginine hydrochloride 600 mg/kg as an IV infusion over 90 to 120 minutes
[1][2][3][4].
Maintenance dose: Sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg in
combination with arginine hydrochloride 600 mg/kg as an IV infusion over 24 hours [1][2][3]
[4].
Known CPS, OTC, or NAGS Deficiency:

Loading dose: Sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg in
[1][2][3][4].
[4].
Known ASS or ASL Deficiency:

Loading dose:Sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg in
[1][2][3][4].
[4].
Repeating the loading dose within 24 hours of the initial loading dose should be
considered only for patients with a severe disorder receiving dialysis[4].
CPS = carbamyl phosphate synthetase; OTC = ornithine transcarbamylase; NAGS = N-acetyl

glutamate synthase; ASS = argininosuccinic acid synthetase; ASL = argininosuccinic acid
lyase
Uses
Adjunctive treatment of acute hyperammonemia in neonates with urea cycle disorders.

Arginine hydrochloride should be used concomitantly with sodium phenylacetate/sodium
benzoate. Hemodialysis is the primary treatment of acute hyperammonemia during the early
management period [1][2][5][3][4]. Caloric supplementation, dietary protein restriction, and
other ammonia lowering therapies should also be considered during acute hyperammonemic
episodes [1].
704
Administration
Must be administered through a central line. For loading and maintenance doses, dilute
sodium phenylacetate/sodium benzoate and arginine in 25 to 35 mL/kg of D10W prior to
administration. Infuse the loading dose over 90 to 120 minutes [1][4].
MEDICATION SAFETY
Caution advised for use in patients with congestive heart failure, severe renal impairment, or
other clinical conditions involving sodium retention with edema; product contains 30.5 mg of
sodium per mL. Extravasation may lead to tissue necrosis; administration through central line
required [1].
Adverse Effects
The most common adverse effects include vomiting (9%), hyperglycemia (7%), and
hypokalemia (7%). Vomiting and lethargy can occur with higher than recommended doses.
Hypotension seen more frequently in patients 30 days of age and less. Potentially life-
threatening toxicity can occur with doses greater than 750 mg/kg per day [1][3].
D10W and arginine hydrochloride 10%.
Monitoring
Measure plasma ammonia levels every hour during dialysis until levels stabilize to less than
200 to 300 micromoles/L. Capillary blood should not be used for monitoring ammonia levels.
Monitor blood glucose, electrolytes (especially potassium), and acid-base status closely
during the acute phase (eg, every 4 hours). Toxicity due to ammonia scavenging drugs
presents as ketoacidosis. An anion gap that is greater than 15 mEq/L or has increased by
greater than 6 mEq/L from baseline may indicate drug accumulation. Monitor amino acids
daily to assess the effectiveness of citrulline/arginine replacement and glutamine removal.
Assess AST and ALT levels [1][3][4]. Evaluate neurological status, Glasgow Coma Scale,
respiratory status, CT or MRI or fundoscopic evidence of cerebral edema, and/or of gray
matter and white matter damage to assess patient response to treatment. Monitor infusion
site closely during infusion for signs of extravasation [1].
705
Pharmacology
The use of sodium phenylacetate and sodium benzoate provides an alternative pathway for
waste nitrogen excretion in patients with urea cycle disorders, attenuating the risk for
ammonia- and glutamine-induced neurotoxicity. Phenylacetate is conjugated with glutamine
via acetylation to form phenylacetylglutamine. Phenylacetylglutamine is excreted by the
kidney and results in removal of 2 moles of waste nitrogen for each mole of phenylacetate
administered. Benzoate is conjugated with glycine to form hippurate. Hippurate is excreted
by the kidney and results in removal of 1 mole of waste nitrogen for each mole of benzoate
administered [1][5][3].
ABOUT
Sodium phenylacetate/sodium benzoate (Ammunol®) is available as a 10%/10% solution in

a single-use glass vial containing 50 mL. Contains 30.5 mg of sodium per mL.
During the admixture process, the Millex® Durapore GV 33 mm Sterile Syringe Filter (0.22
micrometer) provided by the manufacturer must be used when injecting Ammunol® into the
10% dextrose IV bag [1].
706
Sotalol
Dose
To minimize the risk of induced arrhythmia, hospitalize patients initiating or re-initiating

therapy for at least 3 days or until steady-state drug levels are reached, in a facility that can
provide cardiac resuscitation and continuous ECG monitoring. Obtain QT interval and
normalize serum potassium and magnesium prior to initiation. Calculate estimated CrCl to
determine appropriate dosing interval. Withdraw other antiarrhythmic therapy (for a
minimum of 2 to 3 plasma half-lives if possible) prior to initiation [1][2].
Initial dose: 1 mg/kg/dose orally every 12 hours.

Gradually increase as needed every 3 to 5 days until stable rhythm is maintained.
Maximum dose: 4 mg/kg/dose orally every 12 hours.
Uses
Treatment of refractory ventricular and supraventricular tachyarrhythmias.
In adults, sotalol is indicated for the treatment of life-threatening, documented ventricular

arrhythmias, such as sustained ventricular tachycardia. Its use in patients with less severe
arrhythmias, even if the patients are symptomatic, is generally not recommended. Avoid
treatment of patients with asymptomatic ventricular premature contractions [2][1].
In adults, sotalol is indicated for the maintenance of normal sinus rhythm (delay in time to
recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)) in patients with symptomatic
AFIB/AFL who are currently in sinus rhythm. Because sotalol can cause life-threatening
ventricular arrhythmias, reserve its use for patients in whom AFIB/AFL is highly symptomatic.
Patients with paroxysmal AFIB that is easily reversed (by Valsalva maneuver, for example)
should usually not be given Betapace/Betapace AF [2][1].
MEDICATION SAFETY
Contraindicated in patients with sinus bradycardia, sick sinus syndrome, or second and
third degree AV block (unless functioning pacemaker present), congenital or acquired long
QT syndromes, cardiogenic shock or decompensated heart failure, serum potassium less than
4 mEq/L, bronchial asthma or related bronchospastic conditions. For the treatment of atrial
fibrillation/flutter, contraindicated with baseline QT interval greater than 450 milliseconds
or CrCl less than 40 mL/min [1][2].
Cardiovascular: Serious and potentially fatal arrhythmias such as sustained ventricular
707
tachycardia/fibrillation (VT/VF), primarily consisting of Torsade de Pointes (TdP), have been
reported. Higher doses, reduced CrCl, female gender, reduced heart rate and history of
sustained ventricular tachycardia/fibrillation have been associated with increased risk of TdP.
Dose adjustments may be required. Correct hypokalemia or hypomagnesemia prior to
therapy initiation [1][2]
Cardiovascular: Bradycardia or heart block may occur and increase the risk of Torsade de
Pointes [1][2]
Cardiovascular: Significant hypotension may occur [1][2]
Cardiovascular: New onset or worsening heart failure may occur during initiation or dose
increases. Discontinue treatment if symptoms develop [1][2]
Cardiovascular: Exacerbation of angina pectoris and myocardial infarction may occur with
abrupt cessation of beta blocker therapy. Gradual dosage reduction recommended, especially
in patients with ischemic heart disease [1][2].
Concomitant use: Not recommended with drugs that prolong the QT interval [1][2].
Endocrine and metabolic: Hypokalemia or hypomagnesemia can exaggerate the degree of
QT prolongation. Correct imbalances prior to use. Consider acid/base and electrolyte status in
patients with severe or prolonged diarrhea or those receiving concomitant diuretics [1][2]
Endocrine and metabolic: Hyperglycemia may worsen and signs of hypoglycemia may be
masked (eg, tachycardia) in patients with diabetes mellitus [1][2]
Endocrine and metabolic: Exacerbation of hyperthyroidism, including thyroid storm, may
occur upon abrupt withdrawal of beta blocker therapy in patients with thyroid disease. Avoid
abrupt withdrawal. Additionally, beta blockade may mask signs of hyperthyroidism [1][2].
Immunologic: Beta-blocker therapy may cause patients with a history of an anaphylactic
reaction to a variety of allergens to have a more severe allergic reaction on repeated
challenge and to be unresponsive to usual doses of epinephrine [1][2]
Respiratory: Not recommended in patients with bronchospastic diseases. If use is required,
dose adjustment is recommended [1][2].
Surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major
surgery and anesthesia due to the impaired ability of the heart to respond to reflex
adrenergic stimuli may augment risks of general anesthesia and surgical procedures [1][2].
Adverse Effects
Proarrhythmic effects occur in 10% of pediatric patients: sinoatrial block, A-V block, torsades
de pointes and ventricular ectopic activity. These effects usually occur in the first few days of
treatment. Prolongation of the QT interval is dose-dependent. Other adverse effects include
fatigue, dyspnea, and hypotension.
Black Box Warning
To minimize the risk of drug-induced arrhythmia, initiate or reinitiate oral sotalol in a facility
that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Sotalol
can cause life threatening ventricular tachycardia associated with QT interval prolongation. If
the QT interval prolongs to 500 msec or greater, reduce the dose, lengthen the dosing
interval, or discontinue the drug. Calculate creatinine clearance to determine appropriate
dosing [1][2].
708
Monitoring
Frequent EKG during initiation of therapy.
Pharmacology
Sotalol is an antiarrhythmic agent that combines Class II beta-blocking properties with Class
III prolongation of cardiac action potential duration. Betapace® is a racemic mixture of - d
l
and -sotalol. Oral bioavailability is good, but absorption is decreased by 20% to 30% by
food, especially milk. Sotalol does not bind to plasma proteins, is not metabolized, and is
renally excreted as unchanged drug. Limited pharmacokinetic data in infants show a half-life
of 8 hours, increasing significantly in elderly patients and those with renal dysfunction.
ABOUT
Oral solution:
Sotalol 5 mg/mL oral solution is provided in 250 and 480 mL bottles. Store between 20 and
25 degrees C (68 and 77 degrees F), with excursions permitted between 15 and 30 degrees
C (59 and 86 degrees F) [3].
Oral tablets:
Oral formulation supplied in 80-mg, 120-mg, and 160-mg tablets [1][2].
A 5 mg/mL oral suspension may be made as follows: crush 5 (five) 120-mg tablets and add
to 120 mL of OraPlus®:OraSweet® (1:1) or 1% methylcellulose:Simple Syrup NF (1:9) in a
6-ounce amber plastic bottle. Shake to adequately suspend. Stable for 90 days at room
temperature or refrigerated [4][5].
709
Spironolactone
Dose
1 to 3 mg/kg/dose orally every 24 hours.
Uses
Bronchopulmonary dysplasia: Used in combination with other diuretics in the treatment

of BPD (situations of increased aldosterone secretion).
Heart failure (HF): Aldosterone antagonist therapy is reasonable for treatment of chronic
systolic HF when renal function is normal, or mildly impaired. Spironolactone is the typical
agent used as an add-on to ACE inhibitor and beta-blocker therapy when such therapy has
not improved ventricular function or reversed ventricular remodeling [2]. Use is not
recommended in treatment of HF with preserved ejection fraction [3].
Also may be used cautiously for pulmonary hypertension as supportive care in neonates with
signs of right-sided heart failure [4].
Administration
package [1].
[1].
MEDICATION SAFETY
Contraindicated with concomitant use of eplerenone, and in patients with hyperkalemia, or

Addison disease [5].
Precautions
Endocrine and metabolic: Asymptomatic hyperuricemia may occur and rarely precipitate
https://www.micromedexsolutions.com/micromedex2/librarian/CS/17E727/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
710
gout [5].
Endocrine and metabolic: Excessive diuresis may lead to symptomatic dehydration,
hypotension, and worsening renal function with an increased risk in salt-depleted patients or
those taking ACE inhibitors or angiotensin II receptor blockers [5].
Endocrine and metabolic: Gynecomastia may occur and is usually reversible. Risk
increases in a dose-dependent manner [5].
Endocrine and metabolic: Hyperkalemia may occur. Increased risk in patients with
impaired renal function or concomitant use of potassium supplementation, potassium-
containing salt substitutes, or drugs that increase potassium (eg, ACE inhibitors and
angiotensin receptor blockers). Dose adjustment or discontinuation may be necessary [5].
Endocrine and metabolic: Hypomagnesemia, hyponatremia, or hypocalcemia may occur
[5].
Endocrine and metabolic: Hypochloremic alkalosis or hyperglycemia may occur [5].
Renal: Worsening renal function may occur with increased risk in patients taking
concomitant nephrotoxic drugs (eg aminoglycosides, cisplatin, and NSAIDs) [5].
Adverse Effects
Rashes, vomiting, diarrhea, paresthesias, hyponatremia, hypovolemia. Dose-dependent

androgenic effects in females. Gynecomastia in males. Headaches, nausea, and drowsiness.
Use with caution in patients with impaired renal function. May cause false positive ELISA
screening tests for congenital adrenal hyperplasia [5].
Monitoring
Follow serum potassium closely during long-term therapy. Also, measuring urinary potassium
is a useful indicator of effectiveness.
Pharmacology
Competitive antagonist of mineralocorticoids (eg, aldosterone). Metabolized to canrenone

and 7-a-thiomethylspironolactone, active metabolites with extended elimination half-lives.
Decreases excretion of potassium. Highly protein bound. Increases excretion of calcium,
magnesium, sodium, and chloride (small effect). Serum half-life with long term use is 13 to
24 hours. Addition of spironolactone to thiazide diuretic therapy in patients with BPD may
yield little, if any, additional benefit.
ABOUT
711
Suspension
Availability: 25 mg/5mL (5 mg/mL) oral suspension in either a 118- or 473-mL bottle [6].
Storage: Store at a controlled room temperature between 20 and 25 degrees C (68 to 77
degrees F), with excursions permitted between 15 and 30 degrees C (59 to 86 degrees F)
[6].
Tablets
Availability: 25-mg, 50-mg, and 100-mg tablets.
•To prepare 25 mg/mL oral suspension, grind one hundred twenty (120) 25-mg tablets
to a fine powder in a mortar. Add 40 mL of vehicle* and mix to a uniform paste. Then add
the vehicle in geometric portions and mix after each addition. Transfer contents of the
mortar to the calibrated bottle and add enough vehicle to bring the total volume to 120 mL.
Protect from light. Shake well. Suspension is stable for 60 days refrigerated or at room
temperature (at 5 and 25 degrees C).
*Vehicles: 1:1 mixture of Ora-Sweet® and Oral-Plus®; 1:1 mixture of Ora-Sweet SF® and
Oral-Plus®; or cherry syrup (cherry syrup concentrate diluted 1:4 with simple syrup).
•A spironolactone 5 mg/mL suspension, 480 milliliter, may be prepared using 96
spironolactone 25 milligram tablets (Aldactone(R); Searle), distilled water or glycerin to
levigate, Cologel(R) (methylcellulose; Lilly) 160 mL, and a sufficient quantity of a 2:1 simple
syrup/cherry syrup mixture to bring the volume to 480 mL. This mixture should be labeled
"shake well" and "refrigerate" and is stable for 60 days. A spironolactone/hydrochlorothiazide
suspension may be similarly prepared [7].
•A spironolactone 2 mg/mL suspension, 100 milliliters, may be prepared using
spironolactone powder 200 milligrams (Searle), sodium benzoate 100 milligrams, just enough
ethanol 10% to form a paste with the powders, and a sufficient quantity of simple syrup to
bring the volume to 100 mL. This mixture should be labeled "shake well" and is stable for
160 days at room temperature [8].
•A 2.5- or 5-mg/mL oral suspension can be made by crushing five or ten 25-mg
spironolactone tablets, respectively, and suspending the powder in 50 mL of simple syrup.
Suspensions are stable for 1 month refrigerated [9].
double gloves and a protective gown by anyone compounding a hazardous oral liquid or any
hazardous drug for feeding tube. If possible, prepare in a control device. Respiratory, eye,
and face protection are needed if not done in a control device [1].
712
Succinylcholine
Dose
Skeletal Muscle Relaxation/Paralysis

Intravenous
1 to 2 mg/kg IV immediately prior to intubation [1][2][3][4][5][6][7][8]. Repeat doses of 1
mg/kg up to a maximum total dose of 4 mg/kg have been used if muscle relaxation was not
attained by 1 to 3 minutes after administration [4][5].
Must be accompanied by adequate analgesia or sedation [1].
Intramuscular
2 to 4 mg/kg may be given via the IM route only if IV route not accessible [1][3][9].
Uses
Skeletal muscle relaxation/paralysis for neonates requiring rapid sequence intubation or non-
emergent endotracheal intubation [2][3][9][10][4][4][11][5][6][7]. Premedication is
recommended in neonates for all non-emergent intubations if time permits. Premedication
regimens for endotracheal intubation typically include a skeletal muscle relaxant in
combination with an analgesic (an opioid) and/or sedative and a vagolytic agent (usually
atropine) [2][3][10][8][6]. Use of a muscle relaxant without an analgesic agent is not
recommended [3]. Premedication has been shown to decrease the time to successful
intubation and decrease the occurrence of adverse effects (ie, increased intracranial
pressure, hypertension, decreased heart rate and oxygenation) in neonates [4][11][5][8][7].
Use of succinylcholine has resulted in fewer intubation attempts and more successful
intubations compared with no succinylcholine in clinical studies in neonates [10].

Adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle
relaxation during surgery or mechanical ventilation [1].
Administration
May administer undiluted as an IV bolus or further dilute in compatible solution to a

concentration of 1 to 2 mg/mL [1].
MEDICATION SAFETY
713
Contraindicated in the acute phase of injury after multiple trauma, major burns, extensive
denervation of skeletal muscle, or upper motor neuron injury; may result in severe
hyperkalemia, and possible onset of cardiac arrest. Also contraindicated in patients with a
personal or family history of malignant hyperthermia and in patients with skeletal muscle
myopathies [1].
Serious anaphylactic reactions, including fatal cases, have been reported. Bradycardia and
possible asystole may occur; higher risk with second dose; incidence and severity increased
in pediatric patients compared with adults; premedication regimen that includes atropine may
protect against bradyarrhythmias induced by succinylcholine. Hyperkalemia may occur.
Serious cardiac arrhythmias or cardiac arrest due to hyperkalemia may occur in patients with
massive digitalis toxicity or patients with electrolyte abnormalities. Increased risk of severe
hyperkalemia in patients with subarachnoid hemorrhage or chronic abdominal infection, or
conditions causing degeneration of central and peripheral nervous systems [1].
Risk of prolonged neuromuscular blockade in patients with reduced plasma cholinesterase
activity, such as those with genetic abnormalities of plasma cholinesterase (eg, heterozygous
or homozygous for atypical plasma cholinesterase gene) or conditions associated with
pregnancy, severe liver or kidney disease, malignant tumors, infections, burns, anemia,
decompensated heart disease, peptic ulcer, or myxedema. Neuromuscular blockade may also
be prolonged in patients with hypokalemia or hypocalcemia. Prolonged administration may
result in a block resembling a nondepolarizing block (Phase II block). Risk of tachyphylaxis
with repeated use [1].
Malignant hyperthermia has been reported rarely in children who have received
succinylcholine [14][15]; increased risk with coadministration of volatile anesthetics;
monitoring recommended [1].
Intracranial pressure increase (transient) may occur. Increased intraocular pressure has been
reported in patients with narrow angle glaucoma or penetrating eye injury. Intragastric
pressure increase may occur, resulting in regurgitation and possible aspiration of stomach
contents. Initial muscle fasciculations may cause additional trauma in patients with fractures
or muscle spasm [1]. Muscle fasciculations have been rarely reported in children [14].
Adverse Effects
Hypertension, hypotension, prolonged respiratory depression or apnea, jaw rigidity,

postoperative muscle pain, excessive salivation, and rash have been reported [1].
Black Box Warning
Acute rhabdomyolysis with hyperkalemia followed by ventricular dysrhythmias, cardiac arrest,

and death have been rarely reported in seemingly healthy children (usually, but not
exclusively, males, and most frequently 8 years of age or younger) who were subsequently
found to have undiagnosed skeletal muscle myopathy (most frequently Duchenne’s muscular
dystrophy) after administration of succinylcholine chloride [12][13]. This syndrome often
presents as peaked T-waves and sudden cardiac arrest within minutes after the
administration of the drug. Treatment for hyperkalemia should be immediately instituted for
infants or children who appear healthy but develop cardiac arrest, not felt to be due to
inadequate ventilation, oxygenation, or anesthetic overdose after administration of
succinylcholine chloride. Routine resuscitative measures are likely to be unsuccessful;
714
extraordinary and prolonged resuscitative efforts may be required. If there are signs present
for malignant hyperthermia, appropriate treatment should be instituted concurrently. It is
recommended that succinylcholine chloride use in children be restricted to emergency
intubation or instances where immediate securing of the airway is necessary [1].
D5W, D10W, D5LR, D5NS, D5 1/2 NS, NS, 1/2 NS, and LR.
Succinylcholine diluted to 2 mg/mL:

Acyclovir (7 mg/mL), amphotericin B lipid complex (1 mg/mL), argatroban (1 mg/mL),
azithromycin (2 mg/mL), bivalirudin (5 mg/mL), caspofungin (0.5 mg/mL), daptomycin (10
mg/mL), dexmedetomidine (4 mcg/mL), diltiazem (5 mg/mL), ertapenem (20 mg/mL),
granisetron (0.05 mg/mL), levofloxacin (5 mg/mL), linezolid (2 mg/mL), lorazepam (0.5
mg/mL), methotrexate (15 mg/mL), metronidazole (5 mg/mL), milrinone (0.2 mg/mL),
mycophenolate (6 mg/mL), octreotide (5 mcg/mL), ondansetron (1 mg/mL), palonosetron
(0.05 mg/mL), pantoprazole (0.4 mg/mL), piperacillin/tazobactam (40 mg/mL piperacillin),
quinupristin/dalfopristin (5 mg/mL), tacrolimus (0.02 mg/mL), vecuronium (1 mg/mL), and
voriconazole (4 mg/mL).
Succinylcholine diluted to 8 mg/mL:

Amikacin (20 mg/mL), aminophylline (12.5 mg/mL), ampicillin (80 mg/mL in NS only),
ampicillin/sulbactam (80 mg/mL in NS only), atropine (0.5 mg/mL), aztreonam (80 mg/mL),
bumetanide (0.125 mg/mL), calcium chloride (50 mg/mL), calcium gluconate (50 mg/mL),
cefazolin (220 mg/mL), cefotaxime (285 mg/mL), cefotetan (400 mg/mL), cefoxitin (450
mg/mL), ceftazidime (400 mg/mL), ceftriaxone (165 mg/mL), cefuroxime (125 mg/mL),
chloramphenicol (333 mg/mL), cimetidine (24 mg/mL), clindamycin (48 mg/mL),
cyclosporine (2 mg/mL), dexamethasone (12 mg/mL), digoxin (0.125 mg/mL),
diphenhydramine (25 mg/mL), dobutamine (6.25 mg/mL), dopamine (12.8 mg/mL),
enalaprilat (0.625 mg/mL), epinephrine (0.008 or 0.5 mg/mL), epoetin (5000 units/mL),
erythromycin (20 mg/mL), esmolol (40 mg/mL), famotidine (5 mg/mL), fentanyl (25
mcg/mL), fluconazole (2 mg/mL), furosemide (5 mg/mL), gentamicin (6.4 mg/mL), heparin
(1 unit/mL or 160 units/mL), hydralazine (10 mg/mL in NS only), hydrocortisone (62.5
mg/mL), imipenem/cilastatin (5 mg/mL), insulin (50 units/mL in NS only), isoproterenol (0.08
mg/mL), labetalol (2.5 mg/mL), lidocaine (10 mg/mL), magnesium sulfate (250 mg/mL),
methylprednisolone (125 mg/mL), metoclopramide (2.5 mg/mL), metoprolol (0.5 mg/mL),
midazolam (2.5 mg/mL), morphine (4 mg/mL), naloxone (16 mcg/mL), nitroprusside sodium
(0.8 mg/mL), ondansetron (1 mg/mL), papaverine (15 mg/mL), phentolamine (5 mg/mL),
phytonadione (5 mg/mL), piperacillin (320 mg/mL), potassium chloride (1 mEq/mL),
procainamide (250 mg/mL), propranolol (0.5 mg/mL), protamine (5 mg/mL), pyridoxine (50
mg/mL), ranitidine (2 mg/mL), theophylline (4 mg/mL), ticarcillin/clavulanate (195 mg/mL
ticarcillin), tobramycin (6.4 mg/mL), vancomycin (20 mg/mL), vasopressin (4 units/mL), and
verapamil (1.25 mg/mL).
Undiluted Succinylcholine 20 mg/mL:

Heparin (1 unit/mL), hydrocortisone (0.1 mg/mL), potassium chloride (0.04 mEq/mL), and
715
propofol (10 mg/mL).
Amphotericin B, azathioprine, diazepam, diazoxide, ganciclovir, indomethacin, nafcillin,

oxacillin, penicillin G potassium, penicillin G sodium, pentobarbital, phenobarbital, phenytoin,
sodium bicarbonate, and trimethoprim/sulfamethoxazole.
Monitoring
Monitor oxygen saturation, heart rate, and blood pressure continuously [3].
Closely monitor ECG for peaked T-waves, an early sign of potential cardiac arrest secondary
to acute rhabdomyolysis with hyperkalemia. Monitor temperature and expired carbon dioxide
continuously for early recognition of malignant hyperthermia [1].
Pharmacology
Succinylcholine is an ultra short-acting depolarizing-type, skeletal muscle relaxant. Has no

effect on pain threshold, consciousness, or cerebration. Onset of paralysis after IV
administration is 30 to 60 seconds with a duration of action of 4 to 6 minutes [16][17]. Onset
of action after IM administration is 2 to 4 minutes with a duration of action of 19 to 23
minutes [1][18]. Rapidly hydrolyzed by plasma cholinesterase to succinylmonocholine (which
possesses clinically insignificant depolarizing muscle relaxant properties) and then more
slowly to succinic acid and choline. Approximately 10% of the drug is eliminated in the urine
as unchanged drug [1].
ABOUT
Available in 100 mg/mL single-use vials and 20 mg/mL multi-dose vials. Store in refrigerator.
Multidose vials are stable for up to 14 days if stored at room temperature. May be further
diluted in compatible solution to a concentration of 1 to 2 mg/mL. Diluted solutions should be
used within 24 hours of preparation [1][19].
716
Sucrose
Dose
Preterm infants: 0.5 to 1 mL of 12% to 24% sucrose solution.

Term infants: 2 mL of 12% to 24% sucrose solution.
Administer sucrose solution directly to the tongue 2 minutes prior to the painful procedure.
For patients able to suck, a pacifier should be offered immediately after sucrose
administration.
Alternatively, a pacifier dipped in sucrose solution can be offered 2 minutes prior to the
procedure.
Uses
Mild analgesia and behavioral comforting prior to painful procedures (eg, vaccination, heel
lances) in infants [1][2][3][4][5][6][7]. A combination of sucrose plus non-nutritive sucking
was more effective than no intervention and more effective than either single intervention
alone in 180 full-term neonates (greater than 2200 g) older than 24 hours undergoing a
heel-stick procedure. The dose of sucrose was 2 mL of sucrose 30% administered 2 minutes
before the procedure [8].
MEDICATION SAFETY
Adverse Effects
Sucrose 24% has an osmolarity of approximately 1000 mOsm/L. The adverse effects of
repeated doses in premature infants are unknown.
Monitoring
Assess for signs of pain and discomfort.
Pharmacology
717
Sucrose administration provides a calming effect and reduces acute procedural pain in both
preterm and term infants. The potential mechanism of these effects includes activation of the
endogenous opioid system through taste receptors on the tip of the tongue. The time to
maximal effect is approximately 2 minutes and the duration of effect is approximately 5 to 10
minutes. The beneficial effects of sucrose can be improved by nonnutritive sucking.
ABOUT
Sweet-Ease®, a 24% sucrose and water solution, is aseptically packaged in an 15 ml cup

with a peel off lid that is suitable for dipping a pacifier or for administration via a dropper.
718
Surfactant (Natural, animal-derived)
Dose
See specific products (beractant, calfactant, or poractant alfa) for dosing and administration
information.
Uses
Prophylaxis of infants at high risk for RDS (those less than 29 weeks gestation).
Rescue treatment of infants with moderate to severe RDS.
Treatment of mature infants with respiratory failure due to meconium aspiration
syndrome, pneumonia, or persistent pulmonary hypertension.
MEDICATION SAFETY
Adverse Effects
Administration of exogenous surfactants should be restricted to highly supervised clinical

settings, with immediate availability of clinicians experienced with intubation, ventilator
management, and general care of premature infants. Reflux of exogenous surfactant up the
ET tube and falls in oxygenation occur frequently. If the infant becomes dusky or agitated,
heart rate slows, oxygen saturation falls more than 15%, or surfactant backs up in the ET
tube, dosing should be slowed or halted. If necessary, ventilator settings and/or FiO2 should
be turned up. Pulmonary hemorrhage occurs in 2% to 4% of treated infants, primarily the
smallest patients with untreated PDA. This may be due to hemorrhagic pulmonary edema
caused by the rapid fall in pulmonary vascular resistance and resulting increased pulmonary
blood flow.
Monitoring
Assess ET tube patency and position. Oxygen saturation, EKG, and blood pressure should be
monitored continuously during dosing. Assess for impairment of gas exchange caused by
blockage of the airway. After dosing, frequent assessments of oxygenation and ventilation
should be performed to prevent postdose hyperoxia, hypocarbia, and overventilation.
719
Pharmacology
In infants with RDS, exogenous surfactant therapy reverses atelectasis and increases FRC,
with rapid improvements in oxygenation. All preparations reduce mortality from RDS. Natural
surfactants are more effective than synthetics in reducing pulmonary air leak. There are no
significant differences between preparations in chronic lung disease or other long term
outcomes. All commercially available preparations contain surfactant apoprotein C (SP-C),
none contain SP-A. The lung-mince extracts Survanta® and Curosurf® contain less than 10%
of the SP-B contained in the lung-wash extract Infasurf®.
720
Piperacillin/Tazobactam
Dose
Dosing in neonates is based on limited pharmacokinetic studies [1][2][3].

PMA
Postnatal Dose IV * † Interval
(weeks)
29 weeks or less 100 mg/kg/dose
45 weeks or more ALL 100 mg/kg/dose 8 hours
PMA = Postmenstrual age (PMA equivalent to gestational age plus postnatal age). PMA is the
primary determinant of dosing interval, with postnatal age as the secondary qualifier.
*Dose for piperacillin component
† Target concentrations were achieved (unbound piperacillin concentrations for 75% of the
dosing interval) in 78%, 75%, and 90% of dose simulations at MICs of 32 mg/L, 16 mg/L,
and 8 mg/L or less, respectively [2].
Dose Adjustments
Renal impairment
Dosage adjustment is recommended; there are no data available to provide dose
recommendations for neonate patients with renal impairment[4].
Uses

https://doi.org/10.1161/CIR.0000000000000298

Streptococci
Gentamicin (for first enterococci
721
or 2 weeks, or entire Ampicillin +
enterococci course for CefTRIAXone (for
CefTRIAXone +
gentamicin (not for
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)
Baltimore, 2015

Piperacillin/tazobactam is not approved for newborn infants.
In children 2 months or older, it's approved for appendicitis (complicated by rupture or
abscess) and peritonitis caused by piperacillin-resistant, β-lactamase producing strains of
Escherichia coli or the following members of the Bacteroides fragilis
group: , B fragilis B
ovatus B thetaiotaomicron B vulgatus
, , or [4].
Additional approved indications in adults: uncomplicated and complicated skin and skin
722
structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic food
infections caused by β-lactamase producing isolates of Staphylococcus aureus
; postpartum
endometritis or pelvic inflammatory disease caused by β-lactamase producing isolates of E
coli; community-acquired pneumonia (moderate severity only) caused by β-lactamase
Haemophilus influenzae
producing isolates of ; moderate to severe nosocomial pneumonia
caused by β-lactamase producing isolates ofS aureus and by piperacillin/tazobactam-
susceptibleAcinetobacter baumanii H influenzae, Klebsiella pneumoniae
, , and Pseudomonas
aeruginosa ; use concomitant aminoglycoside therapy when treating nosocomial pneumonia
caused by P aeruginosa [4].
Administration
Infuse IV over at least 30 minutes at [5] recommended concentrations in pediatric patients of

40, 60, and 200 mg/mL (piperacillin component) [6].
MEDICATION SAFETY
CONTRAINDICATIONS
Contraindicated in patients with a history of hypersensitivity reactions to any of the
penicillins, cephalosporins, or beta-lactamase inhibitors [4].
PRECAUTIONS
Concomitant Use: Probenecid not recommended unless benefit outweighs risk [4]
Dermatologic: Serious cutaneous reactions (eg, Stevens-Johnson syndrome, toxic
epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and
acute generalized exanthematous pustulosis) have been reported; close monitoring
recommended and discontinue if lesions progress [4]
Endocrine and metabolic: Hypokalemia may occur especially in patients with low
potassium reserves and concomitant diuretic or cytotoxic therapy; monitoring recommended
in patients with low potassium reserves [4]
Endocrine and metabolic: Use caution in patients requiring sodium restriction as product
contains 2.84 mEq (65 mg) of sodium per g of piperacillin [4].
Gastrointestinal: Clostridium difficile-associated diarrhea, including mild diarrhea to fatal
colitis, has been reported and may occur more than 2 months after use; discontinuation of
antibacterial use not directed against C. difficile may be required [4]
Hematologic: Bleeding manifestations have been reported with piperacillin use, especially in
patients with renal failure; monitoring recommended particularly with prolonged use (ie, 21
days or greater); discontinue use if occurs [4]
Hematologic: Leukopenia and neutropenia have been reported, especially with prolonged
use; usually reversible upon discontinuation; however, monitoring recommended [4]
Immunologic: Serious anaphylactic reactions, with some fatal cases, have been reported,
especially in patients with history of penicillin, cephalosporin, or carbapenem hypersensitivity
or history of sensitivity to multiple allergens [4]
Neurologic: Neuromuscular excitability or convulsions may occur at higher than
recommended doses, particularly in the presence of renal failure [8].
Renal: Increased risk of nephrotoxicity in critically ill patients, including renal failure and
723
delayed recovery of renal function; consider alternative therapy, otherwise monitoring
required during treatment [9].
Renal: Use caution in patients with renal failure; increased risk of neuromuscular excitability
or convulsions with higher than recommended IV doses [4]
Renal: Renal insufficiency (ie, CrCl less than or equal to 40 mL/min) and hemodialysis or
continuous ambulatory peritoneal dialysis patients; dosage adjustments required [4]
Respiratory: Use caution in patients with cystic fibrosis due to increased risk for fever and
rash [4]
Adverse Effects
Common adverse events (greater than 5%) in adults were diarrhea, constipation, nausea,
headache, and insomnia [4].
D5W, D10W, NS and LR.
Aminophylline, aztreonam, bumetanide, calcium gluconate, cefepime, cimetidine,

clindamycin, dexamethasone, dopamine, enalaprilat, esmolol, fluconazole, furosemide,
heparin, hydrocortisone succinate, linezolid, lorazepam, magnesium sulfate, metoclopramide,
metronidazole, milrinone, morphine, potassium chloride, ranitidine, remifentanil, sodium
bicarbonate, trimethoprim/sulfamethoxazole, and zidovudine.
Acyclovir, amikacin, amiodarone, amphotericin B, azithromycin, caspofungin, dobutamine,

famotidine, ganciclovir, gentamicin, netilmicin, tobramycin, and vancomycin.
Monitoring
Monitor electrolytes periodically in patients with low potassium reserves. Consider monitoring
electrolytes periodically in patients with potentially low potassium reserves or those receiving
cytotoxic therapy or diuretics. Periodic assessment of hematopoietic function, especially with
prolonged therapy of 21 days or greater [4].
724
Pharmacology
Piperacillin/tazobactam combines the extended-spectrum antibiotic piperacillin with the beta-

lactamase inhibitor tazobactam.
Distribution: Both piperacillin and tazobactam were 30% bound to plasma proteins. Mean
tissue concentrations were typically 50% to 100% of plasma concentrations. In non-inflamed
meninges, distribution of piperacillin and tazobactam into CSF was low [4].
Excretion: Both piperacillin and tazobactam were eliminated by glomerular filtration and
tubular secretion. Piperacillin was excreted rapidly as unchanged drug (68% excreted
unchanged). Tazobactam and its metabolite was eliminated primarily by renal excretion
(80% excreted unchanged) [4].
Neonatal Pharmacokinetics
Gestational Age Postnatal Age CL (L/hr/kg) V (L/kg) Half-life (hours)
younger than 14
0.055 (0.034 to
days 0.42 5.3 (2.1 to 8.6)
0.137)
0.42 2.5 (2.1 to 8.9)
(n=9) 0.142)
younger than 14
0.104 (0.063 to
days 0.42 2.8 (2.1 to 4.6)
0.142)
32 weeks or more (n=8)
0.42 4.5 (1.7 to 4.7)
(n=3) 0.177)
0.085 (0.033 to
Overall (n=32) 0.42 3.5 (1.7 to 8.9)
0.177)
Data are median (range) population parameter estimate
Clearance of piperacillin/tazobactam is significantly associated with body weight,

postmenstrual age, postnatal age, and serum creatinine [2].
The population parameter estimates for piperacillin in 32 neonates administered
piperacillin/tazobactam 240 mg/kg/day (piperacillin component) IV divided every 8 hours (3
of the oldest infants (14 days or older and 32 weeks or more gestational age) received 300
mg/kg/day) administered over 30 minutes is in the tables below [2]:
Cohort Predicted Piperacillin Concentrations at Steady State
Concentration for Concentration for

Gestational Age Postnatal Age Cmin (mg/L) 75% of the dosing 50% of the dosing
interval (mg/L) interval (mg/L)
younger than 14
days 38.3 (7.4 to 48.4) 51.9 (16.9 to 58.9) 71.1 (38.6 to 75.6)
14 days or older
34.6 (5.5 to 48.4) 48.5 (13.5 to 58.9) 69.1 (33.6 to 75.6)
(n=9)
725
32 weeks or more younger than 14 28 (1.3 to 48.4) 41.9 (4.7 to 58.9) 64.3 (17 to 75.6)
days
(n=8)
14 days or older
31.1 (1.5 to 60.2) 48.2 (5.7 to 73.4) 76.6 (20.7 to 94.5)
(n=3)
Overall (n=32) 30.1 (1.3 to 60.2) 44.1 (4.7 to 73.4) 66.2 (17 to 94.5)
Data are median (range)
Target concentrations were achieved (unbound piperacillin concentrations for 75% of the
dosing interval) in greater than 90% of dose simulations at MICs of less than 8 mg/L up to
32 mg/L with the following dosages 100 mg/kg/dose IV every 8 hours for PMA of 30 weeks
or less, 80 mg/kg/dose IV every 6 hours for PMA of 31 to 35 weeks, and 80 mg/kg/dose IV
every 4 hours for PMA 36 to 49 weeks [2].
Extended-infusion (over 2 to 4 hours) did not improve target concentrations compared with
standard infusion (30 minutes) in a model-based simulation in neonates [2].
ABOUT
Available as powder for injection (containing EDTA and sodium citrate) in 2.25-g, 3.375-g,
and 4.5-g single-dose vials and 40.5 g pharmacy bulk vials. Each vial provides 2 g, 3 g, 4 g,
and 36 g of piperacillin for the 2.25-g, 3.375-g, and 4.5-g single-dose vials and 40.5 g
pharmacy bulk vials [10].
Each 2.25-g, 3.375-g, 4.5-g vial, and 40.5-g bulk vial contains 5.68, 8.52, 11.36 mEq, and
100.4 mEq (130, 195, 260, 2304 mg) of sodium, respectively [10].
Reconstitute Stable for 24 hours at room temperature, 48 hours refrigerated:
40.5 g vial with 152 mL (Concentration: 200 mg/mL piperacillin component)
Further dilution required[10]. Recommended concentrations in pediatric patients: 40, 60,

and 200 mg/mL (piperacillin component) [6].
Ambulatory IV infusion pumps. Reconstitute and dilute each dose to a volume of 25 or
37.5 mL with a compatible solution. Stable for 12 hours at room temperature [10].
Also available in Galaxy® containers (containing EDTA and sodium citrate) as 2.25 g/50 mL,
3.375 g/50 mL, and 4.5 g/100 mL [10].
726
THAM acetate
Dose
1 to 2 mmol/kg (3.3 to 6.6 mL/kg) per dose IV.

Dose (of the 0.3 M solution) may be calculated from the following formula:
Dose (mL) = Weight (kg) x Base deficit (mEq/L)
Maximum dose in neonates with normal renal function is approximately 5 to 7 mmol/kg per
24 hours. Clinical studies support only short-term use.
Uses
Treatment of metabolic acidosis, primarily in mechanically ventilated patients with significant

hypercarbia or hypernatremia. Do not use in patients who are anuric or uremic. THAM
is not indicated for treatment of metabolic acidosis caused by bicarbonate deficiency.
Administration
Administer by slow IV infusion over at least 30 to 60 minutes. Rate of infusion should not
exceed 2 mmol/kg in 30 minutes or 5 mmol/kg in 60 minutes [1]. Infusion into a large vein is
recommended (peripheral or umbilical vein may be used) [2][3]. Has also been administered
with 25% to 50% of the calculated dose given intravenously over 5 to 10 minutes with the
remainder given intravenously over 1 to 6 hours [1][4].
MEDICATION SAFETY
Most reports of toxicity in neonates (hypoglycemia, hyperkalemia, liver necrosis) were related
to rapid umbilical venous infusion of high doses of THAM base solutions that were more
alkaline and hypertonic than the THAM acetate solution currently available from Abbott (pH
8.6; osmolarity 380 mOsm/L). Irritating to veins.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/DC6699/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/2
727
No data are currently available on solutions and additives.
Monitoring
Observe IV site closely for signs of extravasation. Follow blood-gas results to assess
therapeutic efficacy. Follow urine output. Monitor for respiratory depression, hypoglycemia,
and hyperkalemia when using several doses.
Pharmacology
THAM (Tris-Hydroxymethyl Aminomethane) is a proton acceptor that generates NH3+ and

HCO3- without generating CO2. The protonated R-NH3+ is eliminated by the kidneys. Unlike
bicarbonate, THAM does not require an open system for CO2 elimination in order to exert its
buffering effect.
ABOUT
Supplied as a 0.3-M solution (1 mmol = 3.3 mL) in a 500-mL single-dose container with no
bacteriostatic agent. Intended for single-dose use and unused portion should be discarded.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/DC6699/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 2/2
728
Ticarcillin/Clavulanate
Dose
Timentin injection is no longer marketed in the United States [1].

75 to 100 mg/kg/dose IV infusion by syringe pump over 30 minutes.


0 to 28 12
≤29
>28 8
0 to 14 12
30 to 36
>14 8
0 to 7 12
37 to 44
>7 8
≥45 ALL 6
Uses
Timentin injection is no longer marketed in the United States [1].

Treatment of non-CNS infections, caused by susceptible β-lactamase producing bacteria,
including many strains of E. coli, Enterobacter, Klebsiella, Haemophilus influenzae, Proteus
mirabilis, Pseudomonas spp., and Staph. aureus.
Administration
Dilute in NS, D5W, or LR to a final concentration of 10 to 100 mg/mL and administer IV over
30 minutes [2].
MEDICATION SAFETY
729
Seizures may occur when administered at very high doses and in the presence of renal
impairment. Sodium content should be considered when treating patients requiring salt
restrictions (4.5 mEq (103.6 mg) of sodium per gram of ticarcillin/clavulanate).
Adverse Effects
Eosinophilia. Hyperbilirubinemia. Elevations in ALT, AST, BUN, and serum creatinine.

Hypernatremia may be exacerbated in ELBW patients.
D5W, LR, and NS.
Aztreonam, cefepime, famotidine, fluconazole, heparin, insulin, milrinone, morphine,

propofol, remifentanil, and theophylline.
Amikacin, azithromycin, gentamicin, netilmicin, sodium bicarbonate, tobramycin, and

vancomycin.
Monitoring
Serum concentrations are not routinely monitored. Assess renal function prior to therapy.
Measure serum sodium concentrations and hepatic transaminases periodically. Observe IV
site for signs of extravasation.
Pharmacology
Timentin® combines the extended-spectrum antibiotic ticarcillin with the β-lactamase

inhibitor clavulanic acid in a 30:1 ratio. Ticarcillin is primarily eliminated unchanged by renal
mechanisms, whereas clavulanate undergoes significant hepatic metabolism. As a result the
mean half-life of ticarcillin in neonates is 4.2 hours compared to a mean half-life of 2 hours
730
for clavulanate. CNS penetration is modest (limited data).
ABOUT
Available as powder for injection in 3.1-g vials. Reconstitute vial by adding 13 mL of sterile
water for injection. Dilute further with a compatible solution to a concentration between 10
and 100 mg/mL. Dilutions are stable for 24 hours at room temperature, 3 days refrigerated
(D5W), and 7 days refrigerated (NS and LR). Frozen dilutions stable for 7 days for D5W and
30 days for NS and LR.
Contains 4.5 mEq (103.6 mg) of sodium per gram of ticarcillin/clavulanate.
731
Tobramycin
Dose

Dosing Chart
PMA Postnatal Dose Interval
(weeks) (days) (mg/kg) (hours)
0 to 7 5 48
≤29* 8 to 28 4 36
≥29 4 24
0 to 7 4.5 36
30 to 34
≥8 4 24
≥35 ALL 4 24
* or significant asphyxia, PDA, or treatment with indomethacin
The above standard dosing regimen attains trough concentrations 1 mg/L or less and 0.5
mg/L or less in 61% and 24%, respectively, of dose simulations (n=5,000). Likewise, peak
concentrations of 5 to 12 mg/L, greater than 12 mg/mL, and less than 5 mg/L were attained
in 88%, 1%, and 11%, respectively, of dose simulations [1].
Uses
Treatment of infections caused by aerobic gram-negative bacilli (eg, Pseudomonas,

Klebsiella, E coli
). Usually used in combination with a β-lactam antibiotic.

https://doi.org/10.1161/CIR.0000000000000298

Streptococci
CefTRIAXone (for
732
course for aminoglycoside (AMG)-
enterococci) resistant enterococci or
CefTRIAXone +
gentamicin (not for
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)

Baltimore, 2015
Sepsis
Optimal treatment for suspected, early-onset sepsis is broad-spectrum antimicrobial coverage
using a combination of ampicillin and an aminoglycoside (usually gentamicin); once a
pathogen is identified, therapy should be narrowed unless synergism is required. Therapy
should be discontinued at 48 hours if the probability of sepsis is low. Duration of treatment is
usually 10 days for bacteremia without an identifiable focus [7].
There was no difference in failure rate between a 7-day vs 10-day duration of empiric
treatment with IV cefTRIAXone and amikacin for culture-proven sepsis in 132 neonates, 1.5
kg or more and gestational age 32 weeks or more, who remitted clinically by day 5 in a
733
randomized study. The follow-up period was 28 days. The median age at presentation was 3
days (2 to 4 days) and 56.8% had early-onset sepsis. The majority of organisms in blood
cultures were Klebsiella
spp. (40.9%), Staphylococcus aureus
(22.7%), spp. Enterobacter
(16.7%), and MRSA (7.6%) [8].
Administration
Intravenous: Dilute in appropriate volume (as small as 25 mL may be used [2]) of NS or

D5W [3] to concentrations of 2, 4, or 10 mg/mL [4] and infuse over 20 to 60 minutes [3].
Administer as a separate infusion from penicillin-containing compounds.
Intramuscular: For the IM route, solution does not need to be further diluted (10 mg/mL)
[5].
IM injection is associated with variable absorption, especially in the very small infant.
MEDICATION SAFETY
Precautions
Concomitant use: Avoid concomitant or sequential use of the inhalation formulation with
drugs that have neurotoxic, ototoxic, or nephrotoxic potential [10]
Dermatologic: Serious and sometimes fatal allergic reactions, including anaphylaxis and
dermatologic reactions (eg, exfoliative dermatitis, toxic epidermal necrolysis, erythema
multiforme, and Stevens-Johnson syndrome) have been reported; discontinue use if occurs
[9]
Dermatologic: Significant absorption leading to neurotoxicity or nephrotoxicity may occur
following local irrigation or application [9]
Immunologic: Cross-sensitivity to other aminoglycoside antibiotics may occur [9]
Immunologic: Topical sensitivity reaction may occur [9]
Immunologic: Overgrowth of nonsusceptible organisms may occur [9]
Immunologic: Clostridium difficile
-associated diarrhea has been reported; discontinuation
may be needed [9]
Immunologic: Contains sodium metabisulfite, a sulfite that may cause allergic-type
reactions (eg, anaphylactic symptoms or asthmatic episodes) in susceptible patients [9]
Neuromuscular: Neuromuscular disorders (eg, myasthenia gravis); aminoglycosides may
aggravate muscle weakness [10]
Neurologic: Neuromuscular blockade and respiratory paralysis may occur in anesthetized
patients who also received neuromuscular blocking drugs (eg, succinylcholine, tubocurarine,
or decamethonium), or large transfusions with citrate-anticoagulated blood; calcium salts
may reverse blockade [9]
Ophthalmic: Not approved for intraocular or subconjunctival use as macular necrosis has
been reported [9]
Otic: Auditory or vestibular dysfunction [10]; particularly with high doses or prolonged
therapy, previous courses of ototoxic therapy, and dehydration; monitoring recommended
[9]
Renal: Use with caution in patients with renal impairment, due to an increased risk of
734
ototoxicity and nephrotoxicity; monitoring recommended [9]
Renal: Nephrotoxicity may occur and discontinuation may be necessary [10]; monitoring
recommended [9]
Reproductive: Pregnancy; may cause fetal harm [10]
Respiratory: Bronchospasm may occur with inhalation tobramycin [10].
Special populations: Reduced serum concentrations may occur in patients with extensive
burns; monitoring recommended [9]
Special populations: Reduced serum concentrations may occur in patients with cystic
fibrosis; monitoring recommended [9]
Adverse Effects
Transient and reversible renal tubular dysfunction may occur, resulting in increased urinary
losses of sodium, calcium, and magnesium. Vestibular and auditory ototoxicity may occur.
The addition of other nephrotoxic and/or ototoxic medications (e.g. furosemide, vancomycin)
may increase these adverse effects. Increased neuromuscular blockade (i.e. neuromuscular
weakness and respiratory failure) may occur when used with pancuronium or other
neuromuscular blocking agents and in patients with hypermagnesemia.
Black Box Warning
Warnings
•Patients treated with tobramycin injection and other aminoglycosides should be under close
clinical observation, because these drugs have an inherent potential for causing ototoxicity
and nephrotoxicity [9].
•Neurotoxicity, manifested as both auditory and vestibular ototoxicity, can occur. The
auditory changes are irreversible, are usually bilateral, and may be partial or total. Eighth
nerve impairment and nephrotoxicity may develop, primarily in patients having preexisting
renal damage and in those with normal renal function to whom aminoglycosides are
administered for longer periods or in higher doses than those recommended. Other
manifestations of neurotoxicity may include numbness , skin tingling, muscle twitching, and
convulsions. The risk of aminoglycoside-induced hearing loss increases with the degree of
exposure to either high peak or high trough serum concentrations. Patients who develop
cochlear damage may not have symptoms during therapy to warn them of eighth-nerve
toxicity, and partial or total irreversible bilateral deafness may continue to develop after the
drug has been discontinued [9].
•Rarely, nephrotoxicity may not become apparent until the first few days after cessation of
therapy. Aminoglycoside-induced nephrotoxicity usually is reversible [9].
•Renal and eighth-nerve function should be closely monitored in patients with known or
suspected renal impairment and also in those whose renal function is initially normal but who
develop signs of renal dysfunction during therapy. Peak and trough serum concentrations of
aminoglycosides should be monitored periodically during therapy to assure adequate levels
and to avoid potentially toxic levels. Prolonged serum concentrations above 12 mcg/mL
should be avoided. Rising trough levels (above 2 mcg/mL) may indicate tissue accumulation.
Such accumulation, excessive peak concentrations, advanced age, and cumulative dose may
contribute to ototoxicity and nephrotoxicity. Urine should be examined for decreased specific
gravity and increased excretion of protein, cells, and casts. Blood urea nitrogen, serum
creatinine, and creatinine clearance should be measured periodically. When feasible, it is
735
recommended that serial audiograms be obtained in patients old enough to be tested,
particularly high-risk patients. Evidence of impairment of renal, vestibular, or auditory
function requires discontinuation of the drug or dosage adjustment [9].
•Tobramycin injection should be used with caution in premature and neonatal infants
because of their renal immaturity and the resulting prolongation of serum half-life of the drug
[9].
•Concurrent and sequential use of other neurotoxic and/or nephrotoxic antibiotics,
particularly other aminoglycosides (e.g., amikacin, streptomycin, neomycin, kanamycin,
gentamicin, and paromomycin), cephaloridine, viomycin, polymyxin B, colistin, cisplatin, and
vancomycin, should be avoided. Other factors that may increase patient risk are advanced
age and dehydration [9].
•Aminoglycosides should not be given concurrently with potent diuretics, such as ethacrynic
acid and furosemide. Some diuretics themselves cause ototoxicity, and intravenously
administered diuretics enhance aminoglycoside toxicity by altering antibiotic concentrations in
serum and tissue [9].
•Aminoglycosides can cause fetal harm when administered to a pregnant woman [9].
D5W, D10W, and NS.
Acyclovir, alprostadil, amiodarone, aztreonam, calcium gluconate, cefoxitin, ceftazidime,

clindamycin, dopamine, enalaprilat, esmolol, fluconazole, furosemide, insulin, heparin
(concentrations less than or equal to 1 unit/mL), linezolid, magnesium sulfate, metronidazole,
midazolam, milrinone, morphine, nafcillin, nicardipine, ranitidine, remifentanil, theophylline,
and zidovudine.
Ampicillin, azithromycin, cefepime, imipenem/cilastatin, indomethacin, heparin

(concentrations greater than 1 unit/mL), mezlocillin, oxacillin, penicillin G, propofol, and
ticarcillin/clavulanate.
Monitoring
Measure serum concentrations when treating for more than 48 hours. Obtain peak
concentration 30 minutes after IV infusion or 1 hour after IM injection, and trough
concentration just prior to the next dose [5]. When treating patients with serious infections
or significantly changing fluid or renal status consider measuring the serum concentration 24
hours after a dose, and use the chart below for the suggested dosing interval. Blood samples
obtained to monitor serum drug concentrations should be spun and refrigerated or frozen as
soon as possible.
736
Therapeutic serum concentrations:

Peak: 5 to 12 mcg/mL (or Cmax/MIC ratio greater than 8:1)
Trough: 0.5 to 1 mcg/mL
24- hour Concentration

Suggested Dosing Intervals
Concentration at Suggested
Half-life
24 hours Dosing Interval
(hours)
(mg/L) (hours)
≤1 ~8 24
1.1 to 2.3 ~ 12 36
2.4 to 3.2 ~ 15 48
≥3.3 -- Measure level in 24 hours
Pharmacology
Mechanism of action: Tobramycin is an aminoglycoside antibiotic that is bactericidal at low

concentrations against most gram-negative bacilli [11].
Dosing recommendations are based on: (1) Higher peak concentrations increase
concentration-dependent bacterial killing; (2) There is a post-antibiotic effect on bacterial
killing, especially when treating concurrently with a β-lactam antibiotic; (3) There may be
less toxicity with less frequent dosing, due to less renal drug accumulation and (4) there may
be a decreased risk for adaptive resistance [12][2].
Inactivation of tobramycin by penicillin-containing compounds appears to be a time-,
temperature-, and concentration-dependent process. This is probably clinically significant
only when penicillin-containing compounds are mixed in IV solutions or when the blood is at
room temperature for several hours before the assay is performed.
Vd: Volume of distribution is increased in patients with patent ductus arteriosus (PDA).
Clearance: Clearance is decreased in patients with PDA.
Half-life: Serum half-life is prolonged in premature and asphyxiated newborns.
ABOUT
Pediatric injectable solution available in a concentration of 10 mg/mL. Also available as 40

mg/mL [5]

737
Topiramate
Dose
Prevention of Hypoxic-ischemic Encephalopathy (HIE), Adjunct to Hypothermia

Combined frequency of mortality and severe neurological disability was not reduced in a pilot
study (n=44) [1].
Uses
Adjunct for neuroprotection against hypoxic-ischemic encephalopathy (HIE):

Combined frequency of mortality and severe neurological disability at 18 to 24 months of age
was not reduced when topiramate was added to whole-body hypothermia in a randomized
pilot study of 44 asphyxiated term-newborns with HIE. The dosage of topiramate was 10
mg/kg/day orally via orogastric tube once daily for the first 3 days of life. No adverse effects
were related to topiramate [1].
Topiramate has been safely used, in concert with deep or mild hypothermia, for HIE in full-
term newborns (n=27). An initial dose of 5 mg/kg (by orogastric tube) was started at
initiation of hypothermia, followed by doses of either 5 mg/kg or 3 mg/kg given on days 2
and 3 [2]. .
Seizure disorders: The addition of topiramate controlled or reduced acute seizure activity
in 4 of 6 term infants having a variety of seizure syndromes refractory to phenobarbital or
phenobarbital + phenytoin in a retrospective review of use in term newborns (n=6). At
follow-up (5 to 11.5 months), 5 of 6 patients were seizure-free on topiramate monotherapy.
Of these 5 patients, 4 received topiramate 10 mg/kg/day; the remaining patient received 3
mg/kg/day [7].

Immediate-release: Indicated for partial-onset or primary generalized tonic-clonic seizures
in patients 2 years or older (initial monotherapy) and ages 2 years or older (adjunctive
therapy). Indicated for seizures associated with Lennox-Gastaut syndrome in patients 2 years
or older. Indicated for the prophylaxis of migraine headache in adolescents 12 years or older.
The efficacy of topiramate in the acute treatment of migraine has not been studied [8][9].
Extended-release: Indicated as initial monotherapy for partial-onset or primary generalized

tonic-clonic seizures in patients 2 years or older (Qudexy® XR) and 6 years or older
(Trokendi XR™) [5][6]. Indicated as an adjunct for seizures associated with Lennox-Gastaut
syndrome, partial-onset, or primary generalized tonic-clonic seizures in patients 6 years or
older (Trokendi XR™) [5] and 2 years or older (Qudexy® XR) [6]. Also indicated for the
prophylaxis of migraine headache in adolescent patients 12 years or older [5][6]
Administration
738
Sprinkle Capsules: May be opened and the sprinkles mixed with water to be administered
via orogastric tube [2][3]. Use mixture immediately. Do not store opened capsules for future
use [3].
package [4].
[4].
MEDICATION SAFETY
Acute myopia, associated with secondary angle-closure glaucoma, has been reported with
topiramate, generally within the first month of use. Hyperthermia and decreased sweating
have been reported, especially in pediatric patients. Metabolic acidosis has been reported,
with an increased risk in patients with conditions or therapies that predispose to acidosis (eg,
renal disease, severe respiratory disorders, status epilepticus, diarrhea, ketogenic diet, or
certain drugs). In patients with or without a history of seizures, topiramate should be
gradually withdrawn to minimize the potential for seizures or increased seizure frequency.
Hyperammonemia with or without encephalopathy may occur with topiramate with or
without concomitant valproic acid [3].
Adverse Effects
When used for neuroprotection in concert with hypothermia for hypoxic-ischemic

encephalopathy (n=27), mild and reversible acidosis was seen in patients receiving deep
hypothermia (DH); metabolic acidosis was not seen with mild hypothermia (MH). In addition,
short-course topiramate did not cause acid-base imbalance, nephrolithiasis, or
ophthalmological concerns [2].
When used for seizure disorders, 3 of 6 term infants had a weight of less than the fifth
percentile, however, these patients also had poor oromotor control [7].
Monitoring
Monitor for hyperthermia and decreased sweating, especially in hot weather. Measure serum
bicarbonate levels at baseline and periodically during treatment. Seizures or increased seizure
frequency should be monitored in patients with or without a history of epilepsy if rapid
withdrawal of topiramate therapy is required. Examination of ammonia levels is
recommended in any patient experiencing unexplained lethargy, vomiting, or changes in
739
mental status, which may be indicative of hyperammonemia with or without encephalopathy
[3].
Pharmacology
Mechanism of action: The exact mechanism of action of topiramate is unknown; however,

4 properties that may contribute to antiepileptic and antimigraine efficacy include a blockage
of voltage-dependent sodium channels, an augmentation of gamma-aminobutyrate acid
(GABA) activity at some subtypes of the GABA-A receptors, antagonism of AMPA/kainate
subtype of the glutamate receptor, and inhibition of the carbonic anhydrase enzyme,
particularly isozymes II and IV [3]. Neuroprotective effects appear to be related to AMPA and
kainate receptor inhibition, blockade of sodium channels, high-voltage activated calcium
currents, carbonic anhydrase isoenzymes, and mitochondrial permeability transition pore
(MPTP) [10].
The average topiramate concentrations were 6.5 to 7 mg/L after the first dose and 12 to 13
mg/L after the third dose in 44 term newborns administered topiramate 10 mg/kg/day orally
with hypothermia. Topiramate concentrations were significantly lower in infants
coadministered phenobarbital [1].
Topiramate serum concentrations and pharmacokinetics varied, based upon the level of
hypothermia and use of concomitant phenobarbital in 13 full-term newborns with hypoxic-
ischemic encephalopathy who received either deep hypothermia (DH; n=5) or mild
hypothermia (MH; n=8) and either topiramate monotherapy (n=6) or with concomitant
phenobarbital (n=7). All patients received a topiramate dose of 5 mg/kg every 24 hours for 3
days, starting with the initiation of hypothermia. Serum concentrations were lower in patients
who received both MH and phenobarbital (NS). The coefficient of variability was greater in
the DH group than the MH group (p=0.005), likely due to more irregular absorption and
elimination. In those patients who attained virtual steady state (n=9), lower AUC, lower
average serum concentration, and a longer half-life were seen in the DH compared with the
MH group (318.1 +/- 101.6 vs 366.2 +/- 48.1 mg/L/hr, 13.25 +/- 4.2 vs 15.26 +/- 2 mg/L,
and 48.82 +/- 4.6 vs 29.03 +/- 23.8 hours, respectively; all NS). Patients who received
concomitant phenobarbital had lower minimum serum concentrations than those on
topiramate monotherapy (8.7 +/- 2.9 vs 11.67 +/- 0.9 mg/L; p=0.032), with lower maximum
and average serum concentrations, lower AUC, shorter half-life, and higher clearance (15.38
+/- 5.3 vs 19.87 +/- 1.9 mg/L, 12.6 +/- 3.7 vs 15.66 +/- 1.6 mg/L, 302.4 +/- 89.7 vs 375.8
+/- 37.4 mg/L/hr, 26.46 +/- 17.7 vs 42.88 +/- 19.1 hours, 17.92 +/- 6.2 vs 13.42 +/- 1.4
mL/kg/hr, respectively; all NS). Serum concentrations within the reference range of 5 to 20
mg/L were achieved in most patients [11].
ABOUT
740
Oral Sprinkle Capsules: Available as 15-mg and 25-mg sprinkle capsules. Store at or
below 25 degrees C (77 degrees F); protect from moisture [3].
Topiramate 6 mg/mL oral suspension is stable for 90 days when refrigerated (preferred) or
stored at room temperature. To prepare 100 mL of topiramate 6 mg/mL [12]:
Crush six 100-mg topiramate immediate-release tablets and triturate to a fine
powder in a mortar.
Levigate powder to a uniform paste with a 1:1 concentration of Ora-Plus®:Ora-Sweet®

vehicle.
Geometrically incorporate vehicle with constant mixing; transfer mixture to a graduated
cylinder.
Rinse mortar with vehicle, transfer to cylinder, and add sufficient vehicle to 100 mL.
Transfer suspension to a plastic prescription bottle; label "Shake Well Before Use" and
"Refrigerate".
double gloves and a protective gown by anyone compounding a hazardous oral liquid or any
hazardous drug for feeding tube. If possible, prepare in a control device. Respiratory, eye,
and face protection are needed if not done in a control device [4].
741
Tropicamide (Ophthalmic)
Dose
1 drop instilled in the eye at least 10 minutes prior to funduscopic procedures.

Use only the 0.5% ophthalmic solution in neonates.
Apply pressure to the lacrimal sac during and for 2 minutes after instillation to minimize
systemic absorption.
Uses
Induction of mydriasis and cycloplegia for diagnostic and therapeutic ophthalmic procedures.
MEDICATION SAFETY
Adverse Effects
Feedings should be withheld for 4 hours following procedure. Systemic effects are those of
anticholinergic drugs: Fever, tachycardia, vasodilatation, dry mouth, restlessness, decreased
gastrointestinal motility, and urinary retention. The use of solutions with concentrations of
1% or greater have caused systemic toxicity in infants.
Monitoring
Monitor heart rate and assess for signs of ileus prior to feeding.
Pharmacology
Anticholinergic drug that produces pupillary dilation by inhibiting the sphincter pupillae
muscle, and paralysis of accommodation. Mydriasis begins within 5 minutes of instillation;
cycloplegia occurs in 20 to 40 minutes. Recovery of accommodation occurs in 6 hours.
Without lacrimal sac occlusion, approximately 80% of each drop may pass through the
nasolacrimal system and be available for rapid systemic absorption by the nasal mucosa.
742
ABOUT
Supplied as ophthalmic solution in 0.5%, and 1% concentrations in 2-, 3-, and 15-mL
dropper bottles. Store away from heat. Do not refrigerate.
A combination eye drop solution ("Caputo drops") may be prepared in a 15-mL bottle with
3.75 mL of cyclopentolate 2%, 7.5 mL of tropicamide 1%, and 3.75 mL of phenylephrine
10%. The final solution contains cyclopentolate 0.5%, tropicamide 0.5%, and phenylephrine
2.5%.
Use within 24 hours, as the solution contains no preservatives.
743
Ursodiol
Dose
10 to 15 mg/kg/dose orally every 12 hours.
Uses
Treatment of cholestasis associated with parenteral nutrition, biliary atresia, and cystic
fibrosis. Also used to dissolve cholesterol gallstones.
Cholestasis: During first course therapy, ursodiol reduced direct bilirubin by 1.89 mg/dL
compared with an increase of 0.76 mg/dL (p = 0.03) for phenobarbital in a retrospective
study of 68 preterm and term newborns with direct bilirubin greater than 3 mg/dL. The
change for all treatment courses were -3.96 mg/dL for ursodiol and +0.28 mg/dL for
phenobarbital. Median dosages were ursodiol 27.43 mg/kg/day enterally and phenobarbital
4.48 mg/kg/day IV [1].
MEDICATION SAFETY
Contraindicated in patients with complete biliary obstruction [2][3].
Adverse Effects
Nausea/vomiting, abdominal pain, constipation, and flatulence.
Monitoring
Hepatic transaminases and direct bilirubin concentration.
744
Pharmacology
Ursodiol is a hydrophilic bile acid that decreases both the secretion of cholesterol from the
liver and its intestinal absorption. It is well absorbed orally. After conjugation with taurine or
glycine, it then enters the enterohepatic circulation where it is excreted into the bile and
intestine. It is hydrolyzed back to the unconjugated form or converted to lithocholic acid
which is excreted in the feces. Serum half-life is 3 to 4 days in adults. Dissolution of
gallstones may take several months. Aluminum-containing antacids bind ursodiol and inhibit
absorption.
ABOUT
Availability: 250-mg and 500-mg tablet and 300-mg capsules.
Extemporaneous Compounds
20 mg/mL
To prepare 255 mL of ursodiol 20 mg/mL: Empty seventeen (17) 300 mg ursodiol capsules
into a mortar and triturate into a fine powder. Using a small amount of vehicle (choice of 1:1
Ora-Sweet/Ora-Plus OR 1:1 methylcellulose 1%/cherry syrup NF), add to powder and mix
into a paste. Continue to add vehicle in geometric portions until close to volume, mixing well
after each addition. Transfer the suspension to a graduate and add vehicle quantity sufficient
to 255 mL. Transfer suspension to prescription bottle; label with "Shake Well Before Use"
and "Refrigerate." Ursodiol 20 mg/mL suspension is stable for 91 days when refrigerated
(preferred) or stored at room temperature.[4].
25 mg/mL
A 25-mg/mL oral liquid suspension may be made by opening ten (10) 300-mg capsules into a
glass mortar. Mix this powder with 10 mL of glycerin and stir until smooth. Add 60 mL of
Ora-Plus® to the mixture and stir. Transfer the contents of the mortar to a glass amber
bottle and shake well. Add a small amount of orange syrup to the mortar and rinse. Pour the
remaining contents into the amber glass bottle. Then add enough simple syrup to make the
final volume 120 mL, for a final concentration of 25 mg/mL. Shake vigorously. Mixture is
stable for 60 days stored at room temperature or refrigerated[5].
50 mg/mL
A 50 mg/mL oral liquid suspension was made by triturating twelve (12) 250 mg tablets into a
glass mortar. 30 mL of Ora-Plus and 30 mL of either strawberry syrup or Ora-Sweet SF was
mixed to a final volume of 60 mL. Strawberry syrup was prepared by mixing 3200 mL of
simple syrup, NF, and 600 mL of strawberry fountain syrup. Mixture is stable for 90 days
refrigerated (3° to 5°C) or room temperature (23° to 25°C) in amber plastic bottles
[6]
60 mg/mL
A 60-mg/mL oral liquid suspension may be made by opening twelve (12) 300-mg capsules
into a glass mortar. Mix with sufficient amount of glycerin to make fine paste, then add
simple syrup for a total final volume of 60 mL. Mixture is stable for 35 days
refrigerated[7].
745
746
ValGANciclovir
Dose
Symptomatic Congenital CMV Infection: 16 mg/kg per dose orally every 12 hours.
Treat for a minimum of 6 weeks; longer-term treatment may be appropriate [1][2]. Studies
have reported continuing prophylaxis for 3 or 6 months [3][4]
Note: Dosing applies only to pharmaceutical grade valGANciclovir. Data are not available for
extemporaneous formulations.
Dose Adjustment for Hematologic Toxicity: If absolute neutrophil count (ANC) less than
500 cells/mm3 (confirm by repeat count), hold drug until ANC greater than 750 cells/mm3. If
the ANC falls again to less than 750 cells/mm3, reduce the dosage by 50%. If ANC again falls
to less than 500 cells/mm3, discontinue the drug [1].
Uses
Symptomatic congenital CMV infections[8][1][2]. There was no difference between a

duration of 6 weeks or 6 months of valGANciclovir in hearing in the better ear from baseline
to the 6-month follow-up in neonates (32 weeks or more gestational age weighing at least
1800 g) with symptomatic congenital CMV disease. However, secondary outcomes (hearing
at 12 months and 24 months and neurodevelopmental scores) were modestly better with 6
months versus 6 weeks of therapy. There was no difference in grade 3 or 4 neutropenia
between the two treatment durations [3].
Administration
Administer with food.Do not break or crush tablets[5].
•Handle and dispose of according to guidelines for antineoplastic drugs; drug is potentially
carcinogenic and mutagenic [6]
•Avoid direct contact of broken or crushed tablets, the powder for oral solution, and the
reconstituted oral solution with the skin or mucous membranes [6].
•The National Institute for Occupational Safety and Health (NIOSH) recommends the use of
package [7].
•NIOSH recommends the use of double gloves and a protective gown by anyone handling a
747
MEDICATION SAFETY
Precautions
Hematologic: Absolute neutrophil count less than 500 cells/mcL, hemoglobin less than 8
g/dL, or platelet count less than 25,000/mcL; do not use [9].
Hematologic: Increased risk for hematologic toxicity in patients receiving myelosuppressive
drugs or irradiation; with a preexisting cytopenia, previous leukopenia with ganciclovir or
other nucleoside analogues, renal impairment, or baseline neutrophil count less than 1,000
cells/mcL; or infants. Monitoring recommended. Consider hematopoietic growth factor
treatment in patients with severe leukopenia, neutropenia, anemia, or thrombocytopenia [9]
Renal: Acute renal failure may occur in patients receiving concomitant nephrotoxic drugs or
in patients with dehydration [9]
Renal: Renal impairment; dosage reduction recommended [9]
Black Box Warning
Hematologic Toxicity, Impairment of Fertility, Fetal Toxicity, Mutagenesis and Carcinogenesis

[9]
Hematologic Toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia,
pancytopenia, and bone marrow failure including aplastic anemia have been reported in
patients treated with valGANciclovir hydrochloride.
Impairment of Fertility: Based on animal data and limited human data, valGANciclovir
hydrochloride may cause temporary or permanent inhibition of spermatogenesis in
males and suppression of fertility in females.
Fetal Toxicity: Based on animal data, valGANciclovir hydrochloride has the potential to
cause birth defects in humans.
Mutagenesis and Carcinogenesis: Based on animal data, valGANciclovir hydrochloride
has the potential to cause cancers in humans.
Monitoring
CBC, including differential, and platelet counts should be monitor frequently, especially in
patients with a history of leukopenia resulting from ganciclovir or other nucleoside analogue
use, in infants, in patients with renal impairment, and in those with neutrophil counts less
than 1000 cells/mcL at the beginning of treatment. Increase monitoring for cytopenias if
therapy with oral ganciclovir is changed to valGANciclovir due to increased plasma
concentrations of ganciclovir after valGANciclovir administration. Monitor renal function
during therapy. Adjust the dose as appropriate for changes in height and body weight [9].
748
Pharmacology
valGANciclovir is a prodrug of ganciclovir that is rapidly converted to ganciclovir after oral

administration by liver and intestinal esterases. Bioavailability is 40% to 60%, and may be
improved by administering with food. Excreted entirely by the kidneys as unchanged drug.
Elimination half-life in infants is 3 hours. Dosing adjustments may be required for infants with
renal impairment.
ABOUT
Availability: Valcyte® is supplied as a white to slightly yellow powder for constitution,

forming a colorless to brownish yellow tutti-frutti flavored solution, which when constituted
with water as directed contains 50 mg/mL valGANciclovir free base. Available in glass
bottles containing approximately 100 mL of solution after constitution. The inactive
ingredients of Valcyte for oral solution are sodium benzoate, fumaric acid, povidone K-30,
sodium saccharin, mannitol and tutti-frutti flavoring.
Reconstitution: Valcyte® for oral solution must be constituted by the pharmacist prior to
dispensing to the patient. To prepare the oral solution measure 91 mL of purified water in a
graduated cylinder. Shake the Valcyte® bottle to loosen the powder. Remove the cap and
add approximately half the total amount of water for constitution to the bottle and shake the
closed bottle well for about 1 minute. Add the remainder of water and shake the closed
bottle well for about 1 minute. This prepared solution contains 50 mg of valGANciclovir free
base per 1 mL.
Storage: Store constituted oral solution under refrigeration at 2 to 8 degrees C (36 to 46
degrees F) for no longer than 49 days. Do not freeze.
ValGANciclovir 30 mg/mL and 60 mg/mL suspension is stable for 35 days when refrigerated
(4 degrees C). To prepare 120 mL of [10]:
30 mg/mL
Place eight valGANciclovir 450 mg tablets into a mortar. Triturate into a fine powder.
In 1 mL increments, add Ora-Plus to the powder, mixing to form a paste.
Through the process of geometric dilution, add a total of 60 mL of Ora-Plus, mixing well
Add the mixture to an amber glass bottle; scrape mortar and pestle for leftover residue
and add to bottle.
Rinse mortar and pestle with 10 mL of Ora-Sweet and add to bottle; repeat the rinsing
process four times.
Add enough Ora-Sweet to the bottle to bring the total volume to 120 mL; shake well.
Label the bottle with "Shake Well Before Use" and "Refrigerate."
60 mg/mL
Place sixteen valGANciclovir 450 mg tablets into a mortar. Triturate into a fine powder.
In 1 mL increments, add Ora-Plus to the powder, mixing to form a paste.
749
Through the process of geometric dilution, add a total of 60 mL of Ora-Plus, mixing well
Add the mixture to an amber glass bottle; scrape mortar and pestle for leftover residue
and add to bottle.
Rinse mortar and pestle with 10 mL of Ora-Sweet and add to bottle; repeat the rinsing
process four times.
Add enough Ora-Sweet to the bottle to bring the total volume to 120 mL; shake well.
Label the bottle with "Shake Well Before Use" and "Refrigerate."
90 mg/mL suspension was stable for at least 125 days when refrigerated (2°to 8°C). To
prepare 225 mL [11]:
Triturate forty-five valGANciclovir 450 mg tablets into a fine powder in a glass mortar.
Slowly add 45 mL of the sodium benzoate solution * and work the powder into a
smooth paste using a pestle. All film coating should dissolve
Add 50 mL of the cherry-chocolate vehicle **, mix well, and transfer to a beaker that
has been calibrated to 225 mL with a graduated cylinder.
Rinse mortar and pestle with two 50 mL portions of the cherry-chocolate vehicle and
transfer the liquid from each rinse into the beaker.
N
10 hydrochloric acid should be added to adjust pH to approximately 3.2. This may
N
require the addition of 0.4 to 0.45 mL of the 10 hydrochloric acid.
Add cherry-chocolate vehicle to bring the final volume to 225 mL.
N
Add more 10 hydrochloric acid, if necessary, to adjust the pH to approximately 3.2
Mix well and transfer the preparation to an amber bottle.
Label "Refrigerate," "Shake Well," and "Cytotoxic Drug Precautions."
* In a glass beaker, dissolve 117 mg of sodium benzoate in 45 mL of Sterile Water for
Irrigation, USP and set aside. Sodium benzoate concentration of the final suspension was
0.1%.
** Using a 500 mL graduated cylinder, add 0.6 mL of artificial cherry flavoring to 300 mL of
simple syrup and dilute to 500 mL with Hershey's chocolate syrup. Preserve with 0.06%
sodium benzoate. Mix well and set aside. Label with expiration date of one year and store in
refrigerator.
double gloves and a protective gown by anyone compounding a hazardous oral liquid or
preparing any hazardous drug for administration by feeding tube. If possible, prepare in a
control device. Respiratory, eye, and face protection are needed if not done in a control
device [7]
750
Vancomycin
Dose
Initial Dose: 10 to 15 mg/kg/dose IV every 6 to 18 hours

When selecting the dose, consider the suspected/infecting organism, institution-specific MIC,
site of infection, and desired trough. Follow-up trough concentrations are necessary due to
the pharmacokinetic variability and unpredictability in neonates.
Initial Dose Intervals
PMA† Postnatal Age† Interval
29 weeks or less
older than 14 days 12 hours
30 to 36 weeks
37 to 44 weeks
45 weeks or more ALL 6 hours
† Postmenstrual age (PMA) is gestational age plus postnatal age.
PMA is the primary determinant of dosing interval with postnatal age as the secondary qualifier.
Renal function and drug elimination are strongly correlated with postmenstrual age.
Initial trough concentrations of 10 to 20 mg/L were demonstrated in 74.1% with a 15
mg/kg/dose and 14% with a 10 mg/kg/dose, regardless of interval, in 88 neonates (97
concentrations) in the intensive care unit [1].
Multiple pharmacokinetic/pharmacodynamic studies evaluated AUC and MIC and determined
vancomycin troughs of around 10 mg/L may be adequate [2][3][4][5] for the treatment of
neonatal gram-positive infections, predominately coagulase-negative staphylococcus [6][7]
[8][9].
Anthrax (as part of combination therapy) [10][11].

Serum creatinine (SCr) less than 0.7 mg/dL: 20 mg/kg IV loading dose; then 15
mg/kg/dose every 12 hours
SCr 0.7 to 0.9 mg/dL: 20 mg/kg IV loading dose; then 20 mg/kg/dose every 24 hours
SCr 1 to 1.2 mg/dL: 20 mg/kg IV loading dose; then 15 mg/kg/dose every 24 hours
SCr 1.3 to 1.6 mg/dL: 20 mg/kg IV loading dose; then 10 mg/kg/dose every 24 hours
SCr greater than 1.6 mg/dL: 20 mg/kg IV loading dose; then 15 mg/kg/dose every 48
hours
(usually oral therapy) for up to 60 days from onset of illness
Uses
Drug of choice for serious infections caused by methicillin-resistant staphylococci (eg, S

aureus and S epidermidis
) and penicillin-resistant pneumococci.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/F6EE8E/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDS… 1/10
751
Anthrax[10]:

imipenem/cilastatin, or vancomycin. If strains are penicillin- susceptible, then penicillin
G (preferred) or ampicillin (alternative).
Plus
Preferred: Clindamycin Alternatives in order of preference: linezolid, doxycycline (not
Clostridium difficileinfection: Young children and infants may be asymptomatically
colonized, but are unlikely to be infected with C difficile. Routine testing for C difficile in
neonates or infants 12 months or younger with diarrhea is not recommended [16] .
Clinical Definition Recommendation

Initial episode, non-severe MetroNIDAZOLE or Vancomycin
Vancomycin +/- IV metroNIDAZOLE (when critical illness is
Initial episode, severe/fulminant
present)
First recurrence, non-severe MetroNIDAZOLE or Vancomycin
Vancomycin
•For 10 days followed by rifAXIMin* for 20 days OR
Second or subsequent
•As a tapered and pulsed regimen
recurrence
OR
Fecal microbiota transplantation (after multiple recurrences)
McDonald, 2017
* Pediatric dosing not available for rifAXIMin; no FDA approved uses for patients younger than 12
years.

https://doi.org/10.1161/CIR.0000000000000298

Streptococci
CefTRIAXone +
gentamicin (not for
752
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)
Baltimore, 2015

Streptococci
753
CefTRIAXone +
gentamicin (not for
disease specialist.
staphylococci) †
Nafcillin or
cephalosporin or
Vancomycin

cephalosporin
for left-sided
staphylococci
CefTRIAXone
tobramycin or
amikacin, depending
on susceptibility)
Baltimore, 2015
Sepsis, Prophylaxis; Catheter Removal: Clinical sepsis rates of 2% were observed when
infants were receiving antibiotics within 12 hours of removing a peripherally inserted central
catheter (PICC) compared with 13% (p=0.03) of infants not on antibiotics within 12 hours of
removal in retrospective chart review (n=196 premature infants). Elective vancomycin 15
mg/kg IV was administered 2 hours prior to catheter removal in 27 out of 48 removals. The
duration of PICC lines was 24.3 days (range, 8 to 67 days). Susceptibility pattern for
vancomycin did not change during the study period [18]. Reductions (11% vs 0%; p=0.021)
in culture-confirmed sepsis were demonstrated in a prospective randomized controlled study
in 88 preterm infants administered cefazolin 1 hour prior to and 12 hours after removal of a
PICC line compared with no antibiotic use [19]. However, this study was criticized for
methodology shortcomings that limit its applicability [20]. Sepsis rates were 10.3% with
removal of a PICC without antibiotics 48 hours prior to removal compared with 1.5%
754
(p=0.002) in neonates on cefazolin/gentamicin at the time of removal of the PICC in a
retrospective study (n=345) [21].
Sepsis
There was no difference in failure rate between a 7-day vs 10-day duration of empiric
treatment with IV cefTRIAXone and amikacin for culture-proven sepsis in 132 neonates, 1.5
kg or more and gestational age 32 weeks or more, who remitted clinically by day 5 in a
randomized study. The follow-up period was 28 days. The median age at presentation was 3
days (2 to 4 days) and 56.8% had early-onset sepsis. The majority of organisms in blood
cultures were Klebsiella
spp. (40.9%), Staphylococcus aureus
(22.7%), spp. Enterobacter
(16.7%), and MRSA (7.6%) [22].
Ventriculitis, Device Associated: All 7 preterm infants (less than 28 weeks gestation)
experienced resolution of ventriculitis with intraventricular vancomycin (5 out of 8 events
were treated with additional IV vancomycin) in a case series. Ventriculitis resolved in a
median of 5.5 days (range, 2 to 31 days). A total of 40 intraventricular vancomycin doses (3,
5, 10, or 15 mg) were administered in 8 ventriculitis events. Intraventricular vancomycin was
administered over 2 minutes as a sterile 10-mg/mL solution at the end of the normal
reservoir tap followed by a 1-mL sterile NS flush of the ventriculostomy reservoir and
catheter. Doses were repeated for CSF concentrations less than 10 mg/L. The longest
intervals to maintain CSF vancomycin concentration above 10 mg/L were 45 hours for 3 mg
(12.8 mg/L), 97 hours for 5 mg (21.4 mg/L), and 114 hours for 10 mg (19.5 mg/L). Only 2
CSF concentrations were available for the 15-mg dose; 230.7 mg/L at 24 hours post-dose
and 44.9 mg/L at 68 hours post-dose. Concomitant IV vancomycin was used in 5 of the 8
events; median vancomycin trough was 6.1 mg/L (range, less than 2 to more than 100
mg/L). Adverse effects due to intraventricular vancomycin were not confirmed. One patient,
with maximum vancomycin CSF concentrations of 24.9 mg/L, experienced bilateral reduced
hearing which necessitated hearing aids. Daily measurement of vancomycin CSF
concentrations are suggested in patients receiving intraventricular vancomycin [23].

Clostridium difficile
-associated diarrhea and staphylococcal enterocolitis in pediatric patients
younger than 18 years of age. Not effective by the oral route for any other
infection[24]. Specific neonatal data were not provided by the manufacturer.
Administration
Intravenous: Administer by intermittent IV infusion over 60 to 120 minutes (no more

than 10 mg/minute) at a concentration not to exceed 5 mg/mL. Concentrations up to
10 mg/mL have been used in fluid restricted patients [12]. Some institutions use standard
concentrations of 5 and 10 mg/mL [13].
Extravasation ManagementNeonatal data are limited to pooled data from 10 case

reports/case series (n=237) and are not specific to vancomycin extravasation; subcutaneous
saline irrigation with or without hyaluronidase infiltration was commonly used. No
standardized management was established. An option for more severe injuries (stages 3 and
4) is subcutaneous irrigation with saline, but this is not advocated as standard treatment.
Conservative management is appropriate for mild extravasation (stages 1 and 2) [14].
Although not neonatal-specific, the following are recommendations for extravasation of acidic
or alkaline agents (vancomycin is acidic with a pH of 4) [15]
General:
755
Stop and disconnect infusion; do not remove the cannula or needle
Attempt to gently aspirate as much extravasated agent as possible; avoid manual
pressure
Remove cannula or needle
Dry heat and elevation
Closely monitor for signs of coagulation and ischemia
Avoid attempt at pH neutralization (vancomycin - pH 4)
Monitor and consider the need for surgical management such as surgical flushing with
normal saline or debridement and excision of necrotic tissue (especially if pain persists
for 1 to 2 weeks). In cases of compartment syndrome, surgical decompression may be
required
Refractory Events:
Hyaluronidase 15 units intradermally along injection site and edematous area. Give as
five, 0.2-mL intradermal injections along extravasation site and edematous tissue.
Inadvertent Intraarterial Administration:
Leave inadvertent intraarterial line in place for diagnostics
Systemic heparin titrated to therapeutic anticoagulant effect.
Stellate ganglion block
MEDICATION SAFETY
Adverse Effects
Nephrotoxicity and ototoxicity: May be enhanced by aminoglycoside therapy [12][36].

The overall rate of acute kidney injury (AKI) was 2.7% in a retrospective chart review in a
neonatal intensive care unit (n=110; mean gestational age 29 weeks, mean birth weight
1200 g). The incidence of AKI increased with higher vancomycin trough concentrations
(p=0.04); 1.38% for less than 10 mg/L, 0% for 10 to 15 mg/L, and 18.18% for greater than
15 mg/L [33]. The use of concurrent furosemide and vancomycin was associated with an
increased risk of acute kidney injury (AKI) (adjusted OR, 3.52; 95% CI, 1.88 to 6.62) in
pediatric patients (0 to 18 years of age) in the intensive care unit in a retrospective study
(n=265). The rate of AKI was 23.4% [37].
Rash and hypotension (red man syndrome): Appears rapidly and resolves within
minutes to hours. Lengthening infusion time usually eliminates risk for subsequent doses.
Neutropenia: Reported after prolonged administration (more than 3 weeks).
Phlebitis: May be minimized by slow infusion and dilution of the drug.
D5W, D10W, and NS.
756
Acyclovir, alprostadil, amikacin, ampicillin, aminophylline, amiodarone, aztreonam, caffeine

citrate, calcium gluconate, caspofungin, cimetidine, enalaprilat, esmolol, famotidine,
fluconazole, heparin (concentrations of 1 unit/mL or less), hydrocortisone succinate, insulin,
linezolid, lorazepam, magnesium sulfate, meropenem, midazolam, milrinone, morphine,
nicardipine, pancuronium bromide, potassium chloride, propofol, ranitidine, remifentanil,
sodium bicarbonate, vecuronium, and zidovudine.
Cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, chloramphenicol,

dexamethasone, heparin (concentrations greater than 1 unit/mL), mezlocillin, nafcillin,
pentobarbital, phenobarbital, piperacillin, piperacillin/tazobactam, ticarcillin, and
ticarcillin/clavulanate.
Monitoring
Auditory Function: To minimize the risk of ototoxicity, auditory function monitoring should
be considered in patients receiving concomitant ototoxic drugs [25].
Laboratory Monitoring: Monitor renal function for nephrotoxicity. Periodic monitoring of
white blood cell count should be done to screen for neutropenia in patients on prolonged
therapy with vancomycin or those who are receiving concomitant drugs that may cause
neutropenia. Monitor for infusion-related events, including hypotension and red man
syndrome [12].
Vancomycin Concentration
Trough: Troughs should be obtained just prior to the next dose under steady state
conditions (approximately just before the fourth dose) and then repeated as clinically
necessary. Trough concentrations (not peak) are the most accurate measure to monitor for
efficacy [26][25]. Due to the variability in pharmacokinetic parameters, peak and trough
concentrations have been recommended to provide more individualized dosing in neonates
[27]. If peak concentrations are measured, draw 60 minutes after end of infusion.
Target Concentration: Neither vancomycin troughs nor AUC have been correlated with
clinical outcomes in neonates [3][28]. Multiple pharmacokinetic/pharmacodynamic studies in
neonates evaluated AUC and MIC and determined vancomycin troughs of around 10 mg/L
(range, 7 to 15 mg/L) for MICs of 1 mg/L or less may be adequate [2][3][4][5] for the
treatment of the most common neonatal gram-positive infections, which is predominately
coagulase-negative staphylococcus [6][7][8][9]. Although, higher troughs have been
recommended in adults and children (older than neonates). For endocarditis in children
(older than neonates), in the presence of MRSA with MIC of greater than 1 mg/L or when
there is a lack of microbiological response, troughs of 15 to 20 mg/L may be required [17].
In adults, many experts recommend a trough of 15 to 20 mg/L when treating MRSA
bacteremia, infective endocarditis, osteomyelitis, meningitis, pneumonia, complicated skin
and soft-tissue infections, or bone/joint infections [26][25][29].
The recommended trough concentration range for adults with less severe infections is 10 to
15 mg/L [25].
757
For shunt infections, consider monitoring CSF vancomycin levels during therapy
to assess drug concentrations (goal: trough, 5 to 10 mg/L) and potential drug
accumulation [30][31][32].
Methicillin-resistant Staphylococcus aureus
isolates with a vancomycin MIC
greater than 2 mg/L (eg, vancomycin-intermediate or vancomycin-resistant S.
aureus [VISA or VRSA]) require alternative therapy [26].
Nephrotoxicity: The use of higher doses to achieve vancomycin trough

concentrations of 15 to 20 mg/L and the association with nephrotoxicity is
conflicting [33][34][35]. The incidence of acute kidney injury (AKI) increased
with higher vancomycin trough concentrations in 110 neonates during a
prospective study (p=0.04); 1.38% for less than 10 mg/L, 0% for 10 to 15 mg/L,
and 18.18% for greater than 15 mg/L [33]. The odds of AKI increased by 16% for
each 5 mg/kg/day increase in vancomycin dose in one pediatric retrospective
study (n=175) [34]. But in another retrospective pediatric study (n=113),
vancomycin trough concentrations of 15 mg/L or more were not associated with
an increased rate of nephrotoxicity [35]. Increased duration of vancomycin
therapy was associated with increased risk of nephrotoxicity in the 2
retrospective studies. The definitions for nephrotoxicity used in these studies may
be one reason for the differences in findings [34][35].
Pharmacology
Mechanism of action: Vancomycin is bactericidal for most gram-positive bacteria,

but bacteriostatic for enterococci. It interferes with cell wall synthesis, inhibits
RNA synthesis, and alters plasma membrane function. Killing activity is primarily
a time-dependent process, not concentration-dependent. MICs for sensitive
organisms are less than or equal to 1 mg/L.
Pharmacokinetics
Poorly absorbed orally. Diffusion into the lung and bone is variable. Minimal
penetration into the CSF in absence of inflamed meninges. Protein binding is
approximately 55% in adults. Mean volume of distribution is 0.3 to 0.9 L/kg in
infants and 0.5 to 0.8 L/kg in children. Elimination is primarily by glomerular
filtration (80% to 90% recovered unchanged in urine), with a small amount of
hepatic metabolism. Higher clearance in pediatrics compared with adults (2 to 3
times higher). Mean half-life of 3 to 4 hours in infants and 2 to 3 hours in children.
Not effectively removed by hemodialysis or peritoneal dialysis [12][36][38][39].
Intermittent Dosing:
Initial Dose Intervals

PMA† Postnatal Age† Interval
29 weeks or less
30 to 36 weeks
37 to 44 weeks 0 to 7 days 12 hours
758
45 weeks or more ALL 6 hours
† Postmenstrual age (PMA) is gestational age plus postnatal age.
PMA is the primary determinant of dosing interval with postnatal age as the secondary qualifier.
Renal function and drug elimination are strongly correlated with postmenstrual age.
Trough concentrations were 10 to 20 mg/L in 60.7% and less than 10 mg/L in
39.3% of 84 initial troughs using the above dosing intervals at doses of 10 or 15
mg/kg/dose (most regimens used 10 mg/kg/dose) in a retrospective study of
neonates in the intensive care unit. Of those initial troughs in the 10 to 20 mg/L
range, 69.7% were 10 to 15 mg/L and 30.3% were 15 to 20 mg/L. A dose of 15
mg/kg/dose, regardless of interval, achieved a trough concentration of 10 to 20
mg/L in 74.1% of 88 neonates (97 vancomycin initial trough concentrations) [1].
The following were the vancomycin trough concentrations in neonates treated
with 10 mg/kg/dose with the above dose intervals [3][40]. A trough
concentration of 5 to 15 mg/L was achieved in 84.1% of neonates treated in a
retrospective analysis (n=76). Only 9.3% had a trough of less than 5 mg/L [3].
Median trough concentrations were slightly above 10 mg/L for dose simulations
in a retrospective population pharmacokinetic analysis. Serum trough
concentrations of 5 to 15 mg/L were achieved in 52% (90% CI 43% to 60%) and
trough concentrations of 15 to 20 mg/L were achieved in 21% (90% CI 14% to
28%) [40].
Continuous Infusion: In a proposed model-based algorithm (based on postnatal

age and body weight), a 10.5 mg/kg loading dose followed by 25 to 60 mg/kg/24
hours was predicted to achieve an AUC24/MIC of greater than 400 when MIC was
less than 1 mg/L [2]. In pharmacokinetic studies in neonates, vancomycin
continuous infusion maintenance doses and target steady state concentrations
were 28.3 mg/kg/day for 15 to 25 mg/L [41], 20 to 50 mg/kg/day for 15 to 25
mg/L [42][43], 30 mg/kg/day for 10 to 30 mg/L [44], and 20 to 30 mg/kg/day
for 10 to 25 mg/L [45]. Some used loading doses of 10 to 20 mg/kg [41][43][44].
More infants administered continuous infusion vancomycin achieved target
concentrations at the first steady-state level compared with infants administered
vancomycin by intermittent infusion (85% vs 41%; p less than 0.001) in a
randomized trial (n=111; mean birth weight 2271 g; mean gestational age 34
weeks, mean postnatal age 23 days). Target concentrations were 15 to 25 mg/L
for continuous infusion and a trough of 10 to 20 mg/L for intermittent infusion.
The mean time to target concentrations were 27.1 hours for continuous infusion
and 33.6 hours for intermittent infusion [42].
ABOUT
Injection: 500-mg and 1-g vials. Reconstitute 500-mg and 1-g vial with 10 mL
and 20 mL of sterile water for injection, respectively, to make a final
concentration of 50 mg/mL. Reconstituted solution stable for 4 days refrigerated.
Dilute prior to administration using D5W or NS to a maximum concentration of 5
mg/mL (concentrations up to 10 mg/mL may also be used in fluid restricted
patients) [12].
759
Powder for oral solution: 3.75 g (147 mL diluent), 7.5 g (295 mL diluent), 7.5 g
(145 mL diluent), 10.5 g (203 mL diluent), and 15 g (289 mL diluent). Store prior
to reconstitution refrigerated at 2 to 8 degrees C (36 to 46 degrees F). Following
reconstitution, store at 2 to 8 degrees C for up to 14 days. Do not freeze. Protect
from light [24].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/F6EE8E/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELD… 10/10
760
Varicella-zoster Immune Globulin
Dose
Prevention or Attenuation of Varicella Infection

Administer a single dose as soon as possible, ideally within 96 hours of exposure, for
greatest effectiveness [1]. May be administered up to 10 days following exposure [2][3].
Administer a second full dose if additional exposures occur more than 3 weeks following
initial dose [2][4][1].
2 kg or less: Single dose of 62.5 international units (one-half vial) IM [1].
Greater than 2 kg: Single dose of 125 international units (one vial) IM [1].
Uses
Post-exposure prophylaxis of varicella. The decision to administer varicella zoster immune

globulin depends 3 factors: 1) lack of evidence of immunity, 2) whether exposure is likely to
result in infection, and 3) whether the patient is at greater risk for complications than the
general population. The following neonatal patients should receive varicella zoster immune
globulin following exposure [2][4]:
Immunocompromised patients
Neonates whose mothers have signs and symptoms of varicella from 5 days before to 2
days after delivery
Premature infants, exposed anytime during entire period for which they require hospital
care for their prematurity, born at 28 weeks of gestation or greater whose mothers do
not have evidence of immunity
Premature infants, exposed anytime during entire period for which they require hospital
care for their prematurity, born at less than 28 weeks of gestation or who weigh 1000 g
or less at birth, regardless of maternal immunity
Varicella zoster immune globulin is not recommended for healthy, full-term infants who are
exposed postnatally, even if their mothers have no history of varicella infection [4].
Any patient who received varicella zoster immune globulin to prevent varicella infection
should receive varicella vaccine, unless contraindicated, at the recommended age [4].

Indicated for post-exposure prophylaxis of varicella in high-risk individuals. High-risk groups
include [1]:
Premature infants
Newborns of mothers having varicella shortly before or after delivery
Infants less than 1 year old
Immunocompromised patients
Pregnant females
761
Administration
Administer by IM injection only, into the anterolateral aspects of the upper thigh. To avoid
sciatic nerve injury, do not use the gluteal region for injection [1].
The final concentration of each vial is 100 international units/mL when each vial is
reconstituted with 1.25 mL of diluent[1].
MEDICATION SAFETY
Contraindicated in IgA-deficient patients with antibodies against IgA and history of

hypersensitivity to avoid a possible anaphylactoid reaction [1].
In patients with severe thrombocytopenia or any coagulation disorder that would

contraindicate IM injection, only administer if the expected benefits outweigh the potential
risks. Thrombotic events may occur; those at risk include those with multiple cardiovascular
risk factors, impaired cardiac output, coagulation disorders, prolong period of immobilization,
and/or know-suspected hyperviscosity [1].
Adverse Effects
The most common adverse effects observed in clinical trials and patients are injection site
pain (2%) and headache (2%). Less common adverse effects include chills, fatigue, rash,
and nausea [1].
Pharmacology
Sterile preparation of purified human IgG prepared from plasma donated by healthy,
screened donors with high titers of antibodies to the varicella zoster virus (VZV), the
causative agent of chickenpox. Provides passive immunization for non-immune individuals
exposed to VZV, thereby reducing the severity of varicella infection. In volunteers, the mean
peak concentration of varicella antibodies occurs within 5 days of administration. [1].
ABOUT
762
Available as a kit with a glass vial containing approximately 125 international units of freeze-
dried varicella zoster virus antibodies and a single dose vial of 8.5 mL of sterile diluent.
Reconstitute with only 1.25 mL of diluent for a final concentration of 100 international
units/mL. Discard the remaining sterile diluent. Store under refrigeration and do not freeze;
Do not use solution that has been frozen. Do not use after expiration date. May store
reconstituted solution for up to 12 hours under refrigeration prior to use. Partially used vials
should also be discarded [1].
763
Vecuronium
Dose
0.1 mg/kg (0.03 to 0.15 mg/kg) IV push, as needed for paralysis. Usual dosing interval is 1
to 2 hours. Adjust dose as needed based on duration of paralysis.
Uses
Skeletal muscle relaxation/paralysis in infants requiring mechanical ventilation. Proposed

desirable effects are improved oxygenation/ ventilation, reduced barotrauma, and reduced
fluctuations in cerebral blood flow.
Administration
Must be accompanied by adequate analgesia and/or sedation[1].

Administer IV push over 5 to 10 seconds. For continuous IV infusion, may dilute in
compatible diluent to a concentration of 0.1 to 0.2 mg/mL [1][2][3], or infuse undiluted at a
concentration of 1 mg/mL.
MEDICATION SAFETY
Adverse Effects
Hypoxemia may occur because of inadequate mechanical ventilation and deterioration in

pulmonary mechanics. When used alone, cardiovascular side effects are minimal; however,
decreases in heart rate and blood pressure have been observed when used concurrently with
narcotics.
Black Box Warning
According to the manufacturer's black box warning, vecuronium should be administered by

adequately trained individuals familiar with its actions, characteristics, and hazards.
https://www.micromedexsolutions.com/micromedex2/librarian/CS/0BBFB6/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
764
D5W, LR, and NS.
Alprostadil, aminophylline, amiodarone, cefazolin, cimetidine, dobutamine, dopamine,

epinephrine, esmolol, fentanyl, fluconazole, gentamicin, heparin, hydrocortisone succinate,
isoproterenol, linezolid, lorazepam, midazolam, milrinone, morphine, nicardipine,
nitroglycerin, nitroprusside, propofol, ranitidine, trimethoprim-sulfamethoxazole, and
vancomycin.
Diazepam, furosemide, ibuprofen lysine, and micafungin.
Monitoring
Monitor vital signs frequently, blood pressure continuously. Use some form of eye lubrication.
Pharmacology
Nondepolarizing muscle-relaxant that competitively antagonizes autonomic cholinergic

receptors. Sympathetic stimulation is minimal. Vecuronium is metabolized rapidly in the liver
to 3-desacetyl-vecuronium, which is 50% to 70% active, and is excreted renally. Newborns,
particularly premature infants, are especially sensitive to vecuronium; this sensitivity
diminishes with age. Onset of action is 1 to 2 minutes; duration of effect is prolonged with
higher doses and in premature infants. Skeletal relaxation/paralysis is reversed by
neostigmine and atropine.
Factors affecting duration of neuromuscular blockade:
Potentiation: Acidosis, hypothermia, neuromuscular disease, hepatic disease,
cardiovascular disease, aminoglycosides, hypokalemia, hypermagnesemia, renal failure, and
younger age.
Antagonism: Alkalosis, epinephrine, and hyperkalemia.
Sensation remains intact; analgesia should be used for painful procedures.
ABOUT
765
Available as powder for injection in 10-mg and 20-mg vials. Reconstitute 10 mg-vial with 10
mL of compatible solution (1 mg/mL). After reconstitution- 24 hrs stability in refrigerator.
Single use only, discard unused portion. After dilution, use within 24 hours after admixing.
A 0.4-mg/mL dilution may be made by diluting 1 mL of 1-mg/mL concentration with 1.5 mL
of preservative-free normal saline. Dilution is stable for 24 hours in refrigerator.
766
Vi-Sol® Multivitamin Products
Dose
1 dropperful (1 mL) every 24 hours, or as directed by physician.
Vi-Sol® Products
Tri-Vi-Sol ® Poly-Vi-Sol ® Poly-Vi-Sol ®
Multivitamin Multivitamin Multivitamin
Drops Drops with Iron Drops
Amount Amount Amount
Vitamins
A (IU/mL) 750 750 750
D (IU/mL) 400 400 400
C (mg/mL) 35 35 35
E (IU/mL) 5 5
Thiamine (B 1) (mg/mL) 0.5 0.5
Riboflavin (B 2) (mg/mL) 0.6 0.6
Niacin (mg/mL) 8 8
B 6 (mg/mL) 0.4 0.4
B 12 (mcg/mL) 2 *0
Minerals
Iron (mg/mL) **10
*Iron product contains no vitamin B12 due to instability with iron and vitamin C concentrations.
**From ferrous sulfate heptahydrate 50 mg
https://www.micromedexsolutions.com/micromedex2/librarian/CS/A490BB/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/1
767
Vitamin A
Dose
Vitamin A Deficiency - VLBW and ELBW Neonates: 5000 units IM 3 times weekly for 4
weeks [1].
Uses
To reduce the risk of chronic lung disease in high risk premature neonates with vitamin A
deficiency[3][4][1][5]. A moderate reduction in bronchopulmonary dysplasia at the
postmenstrual age of 36 weeks was demonstrated in the vitamin A group compared with the
control group in a meta-analysis (n=4 studies, 1,011 extremely low birth weight infants (birth
weight of less than 1 kg)); risk reduction, 0.88 (95% CI, 0.77 to 0.99). There were no
differences in neonatal death before 1 month, oxygen use at 28 days in survivors, duration of
mechanical ventilation, frequency of any grade intraventricular hemorrhage, retinopathy of
prematurity, or necrotizing enterocolitis in the vitamin A group compared with the control
group. Dosages were 5,000 international units (water-soluble retinyl palmitate) IM 3 times
weekly for 4 weeks, 5,000 international units/kg/day orally for 28 days, and 10,000
international units IM 3 times weekly starting at day 2 for a minimum of 2 weeks or until
initiation of oral feeds [6]. In the NICHD-sponsored trial, 14 infants needed to be treated to
prevent 1 case of chronic lung disease [1]. In a follow-up study of this trial, there were no
significant differences in neurodevelopmental outcomes or mortality at 18 to 22 months
corrected age between infants receiving vitamin A and controls; however, the original trial
was not adequately powered to confirm these follow-up endpoints [7].
Retinopathy of Prematurity (ROP): Vitamin A may reduce the incidence of ROP. More
data are needed in severe ROP to determine the benefit of vitamin A [8].
Administration
Do not administer IV. Administer IM using a 29-g needle and insulin syringe [2].
MEDICATION SAFETY
Adverse Effects
See monitoring section. Concomitant vitamin A (particularly larger doses) and glucocorticoids
(particularly dexamethasone) should be used cautiously as significant, short-term increases
in plasma concentrations of retinol and retinol binding protein can occur [9][10][11]. Preterm
768
neonates from these studies were not receiving the high doses of vitamin A recommended
while receiving dexamethasone therapy.
Monitoring
Assess regularly for signs of toxicity: full fontanel, lethargy, irritability, hepatomegaly, edema,
mucocutaneous lesions, and bony tenderness. Consider measuring plasma retinol
concentrations if available, especially if patient is also receiving glucocorticoid therapy.
Desired concentrations are approximately 30 to 60 mcg/dL [5].
Concentrations less than 20 mcg/dL indicate deficiency, while those greater than 100 mcg/dL
are potentially toxic [5].
Pharmacology
The pulmonary histopathologic changes of BPD and Vitamin A deficiency are remarkably
similar. Vitamin A is the generic name for a group of fat soluble compounds which have the
biological activity of the primary alcohol, retinol. Retinol metabolites exhibit potent and site-
specific effects on gene expression and on lung growth and development. Retinol is supplied
in the diet as retinyl esters [5].
ABOUT
Available as Aquasol A® Parenteral (water-miscible vitamin A palmitate) 50,000 units per mL,
equivalent to 15 mg retinol per mL, in 2-mL vials. Protect from light. Store refrigerated at
36 to 46 degrees F (2 to 8 degrees C). Do not freeze [2].
769
Vitamin D
Dose
Supplementation (for neonates exclusively breastfed or supplemented with infant

formula)
Less than 2000 g: 200 to 400 international units per day orally. When weight is about 1500
g and the infant is tolerating full enteral nutrition, dose can be increased to 400 international
units/day [1].
2000 g or more: 400 international units per day orally [1][2].
Treatment of vitamin D deficiency: 1000 international units per day orally.
Uses
Prevention and treatment of vitamin D deficiency: For breastfed infants, the AAP
recommends that supplementation should begin within the first few days of life, regardless of
whether the infant is exclusively breastfed or supplemented with infant formula. Exclusively
formula-fed infants receiving at least 1000 mL/day of formula receive adequate amounts of
vitamin D without supplementation [1].
Dose comparison: Median vitamin D concentrations were 22 ng/mL for placebo, 39 ng/mL
for 200 international units, and 85 ng/mL for 800 international units (p less than 0.05) of oral
vitamin D supplementation for 28 days in 100 newborns (23 to 27 weeks of gestation; mean
weight 770 g) in a randomized, double-blinded, placebo-controlled trial. The mean number of
days alive and off respiratory support at day 28 were 6.8 +/- 9.5 for placebo, 5.5 +/- 9.1 for
200 international units, and 7 +/- 10.3 for 800 international units (p=0.78) [3]. At 2 years of
age, cognitive scores, neurodevelopment, language, and respiratory outcomes were not
different between vitamin D and placebo (n=70). Although underpowered, 800 international
units of vitamin D did not result in improvement in any outcomes at 2 years of age compared
with 200 international units or placebo [4].
Some data indicate that administration of high doses of vitamin D (4000 to 6400 international
units daily) to breastfeeding mothers is capable of raising 25(OH)-D levels in the infant to
levels similar to those seen with infant supplementation without causing hypervitaminosis D
in the mother [5][6][7].
Fortified mature human milk (24 kcal/oz) provides 283 to 379 international units/day,
preterm formulas (24 kcal/oz) provide 290 to 468 international units/day, and transitional
formula (22 kcal/oz) provides 125 to 127 international units/day of vitamin D in neonates
(weighing more than 1500 g) with intakes of 160 mL/kg/day [1].
Rickets: In enterally fed preterm infants with radiologic evidence of rickets, maximize
nutrient intake by increasing human milk fortifier and/or volume of preterm formula. If
maximization cannot be tolerated, then supplementation with elemental calcium and
phosphorus is recommended. Vitamin D status should be evaluated and target 25-
hydroxyvitamin D concentrations of greater than 20 ng/mL (50 nmol/L) [1].
https://www.micromedexsolutions.com/micromedex2/librarian/CS/3E78CE/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/3
770
MEDICATION SAFETY
Most liquid preparations contain propylene glycol[9].
Adverse Effects
Signs of vitamin D toxicity include hypercalcemia, azotemia, vomiting, and nephrocalcinosis.

A 25(OH)-D concentration greater than 250 nmol/L may be associated with a risk for vitamin
D intoxication.
Monitoring
Signs of vitamin D deficiency include symptomatic hypocalcemia (including seizures), growth

failure, irritability, lethargy, and increased susceptibility for respiratory infections. A 25-
hydroxyvitamin D (25(OH)-D) concentration of less than 50 nmol/L is thought to be indicative
of vitamin D deficiency in infants [2][8][5].
Biochemical monitoring of bone mineral content should be performed in very low birth weight
(less than 1500 g) infants starting 4 to 5 weeks after birth [1].
Pharmacology
The main source of vitamin D is vitamin D3, which is synthesized in the skin through
exposure to ultraviolet B (UV-B) radiation. UV-B in the range of 290 to 315 nm initiates the
synthesis of vitamin D3 by converting 7-dehydrocholesterol into previtamin D3, which is
further converted to vitamin D3. Vitamin D3 binds to vitamin D-binding protein and is
transported to the liver for 25-hydroxylation to 25(OH)-D (calcidiol). Calcidiol undergoes
further hydroxylation in the kidney and other tissues to calcitriol (1,25-dihydroxyvitamin D)
(1,25-OH2-D), the active form of vitamin D. Calcitriol stimulates the intestinal absorption of
calcium and phosphorous, renal reabsorption of filtered calcium, and mobilization of calcium
and phosphorous from bone. As a supplement, vitamin D3 has been shown to be more
effective in raising 25(OH)-D levels when compared with vitamin D2.
ABOUT
771
Vitamin D supplements are available as vitamin D2 (ergocalciferol; plant derived) and vitamin
D3 (cholecalciferol; animal derived).
All liquid vitamin D products contain propylene glycol Refer to the specific manufacturer for
2 .
the amount of propylene glycol [9].
®
•Drisdol (ergocalciferol oral solution) contains 200 units (5 mcg) vitamin D2 per drop. The
inactive ingredient is propylene glycol (1036 mg/mL) [10].
•Baby D drops™ (cholecalciferol liquid vitamin supplement) is supplied as 400 units vitamin
D3 per drop. The inactive ingredient is purified palm-kernel oil.
•Bio-D-Mulsion™ (cholecalciferol; emulsified vitamin D3) is supplied as 400 units per drop.
Inactive ingredients include water, sesame oil and acacia.
•Just D (cholecalciferol) is supplied as 400 units vitamin D3 per mL. The inactive ingredient is
corn oil.
•Enfamil® D-Vi-Sol™ (cholecalciferol) is supplied as 400 units vitamin D3 per mL. Inactive
ingredients include glycerin, water, polysorbate 80, citric acid, sodium citrate, sodium
hydroxide, artificial flavor and artificial caramel color.
•Aqueous Vitamin D Oral Drops (cholecalciferol) 10 mcg/mL. Contains glycerin, water and
polysorbate 80 [11]
772
Vitamin E
Dose
5 to 25 units per day orally. Dilute with feedings. Do not administer simultaneously with iron;
iron absorption is impaired.
Uses
Prevention of vitamin E deficiency. May be indicated in babies receiving erythropoietin and

high iron dosages. Higher doses used to reduce oxidant-induced injury (ROP, BPD, IVH)
remain controversial.
MEDICATION SAFETY
Adverse Effects
Feeding intolerance may occur due to hyperosmolarity of preparation. Pharmacologic doses

of alpha tocopherol have been associated with increased rates of sepsis (antioxidant effect of
drug) and NEC (osmolarity of oral formulation).
Monitoring
Assess feeding tolerance. Signs of vitamin E deficiency include hemolytic anemia and
thrombocytosis. Physiologic serum vitamin E concentrations are between 0.8 and 3.5 mg/dL.
Pharmacology
Alpha-tocopherol is the most active antioxidant of the group of tocopherols known as vitamin
E. The amount required by the body is primarily dependent upon the dietary intake of fat,
especially polyunsaturated fatty acids (PUFA). Human milk and currently available infant
formulas contain adequate vitamin E and have appropriate E:PUFA ratios to prevent
hemolytic anemia. Infants receiving supplemental iron amounts above 2 mg/kg/day may also
require additional vitamin E. Oral absorption of vitamin E is dependent upon hydrolysis that
773
requires bile salts and pancreatic esterases. This can be quite variable in very immature
infants and those with fat malabsorption. Free tocopherol is absorbed in the small intestine,
taken via chylomicrons into the gastrointestinal lymphatics, then carried via low-density
lipoproteins to be incorporated into cell membranes. Significant tissue accumulation may
occur with pharmacologic doses.
ABOUT
Available as liquid drops: Aquavit E® (Hospira), 15 units (equivalent to 15 mg) per 0.3 mL.
Also contains polysorbate 80, propylene glycol, sorbitol, saccharin, and artificial flavor.
Hyperosmolar (3620 mOsm/kg H2O). Store at controlled room temperature.
774
Vitamin K1
Dose
Vitamin K deficiency bleeding, Prophylaxis for early and late bleeding

Intramuscular
0.5 to 1 mg [1][2][3][4] IM at birth [2][3][4]; infants more than 1500 g, 1 mg IM within 6
hours after birth and infants 1500 g or less, 0.5 mg IM within 6 hours after birth [2]
Oral (when IM route refused)

IM is the preferred route
[5][6]. Oral route is an acceptable alternative when the IM route is
refused by the parents Avoid the oral route in infants who are premature, ill, or unable
[2].
to take oral vitamin K; have cholestasis or impaired intestinal absorption; or were exposed to
drugs that interfere with vitamin K metabolism through their mothers [5].
Guidelines Dosage
2 mg orally at birth followed by 1 mg orally once weekly for 3 months [5][7]
OR 2 mg orally at birth followed by 2 mg orally at 4 to 6 days and at 4 to 6 weeks [5]
OR 2 mg orally at the first feeding followed by 2 mg orally at 2 to 4 weeks of age and 6 to 8
weeks of age [2].
Vitamin K deficiency bleeding (VKDB), Treatment:

Subcutaneous route is preferred. When IV administration is unavoidable, inject slowly (not to
exceed 1 mg/minute)[1]. Avoid IM route in the presence of coagulopathy[8]
1 mg subQ, IM [1], or IV [1][8]. Higher doses may be necessary in infants whose mothers
have been receiving oral anticoagulants [1].
In observational studies of infants with early, classical, or late VKDB, single doses of 1 to 10
mg IV were used [9][10]. Daily doses of 1 to 5 mg IV for a mean of 3.7 days have also been
used [11]. .
Uses
Vitamin K deficiency bleeding (VKDB); Prophylaxis for early and late bleeding
(hemorrhagic disease of the newborn): The preferred route is intramuscular [2][5][3][13][7]
[4]. The oral route should be used only in circumstances when there are shortages of the
parenteral form [7] or the injection is refused by the parents [2]. Observational studies in
other countries of exclusively breast-fed infants on oral regimens identified the lowest
prevalence of late VKDB with durations of vitamin K for at least 3 months [7].
Vitamin K deficiency bleeding: Bleeding resolves within a few hours after IV
administration of vitamin K1[8][14].

Prophylaxis and treatment of vitamin K deficiency bleeding in neonates [1]
775
Administration
Intravenous
•Administer at concentrations of 1, 2, or 10 mg/mL [12] slowly not to exceed 1
mg/minute . [1].
•Whenever possible, administer benzyl alcohol-free formulations [1].
MEDICATION SAFETY
Dermatologic: Cutaneous reactions, including eczematous reactions, scleroderma-like

patches, urticaria, and delayed-type hypersensitivity reactions, have been reported with
onset ranging from 1 day to a year after therapy; discontinue use if skin reactions occur [1]
Immunologic: Hypersensitivity reactions have included shock, cardiorespiratory arrest,
flushing, diaphoresis, chest pain, tachycardia, cyanosis, weakness, and dyspnea and have
occurred despite dilution and upon first dose [1]
Special populations: Serious adverse reactions including "gasping syndrome" have been
reported in neonates and infants due to benzyl alcohol content. Consider the combined daily
metabolic load of benzyl alcohol from all sources. The minimum amount of benzyl alcohol at
which serious adverse reactions can occur is unknown [1].
Adverse Effects
Severe reactions, including death, have been reported with IV administration in adults. These
reactions are extremely rare, and have resembled anaphylaxis and included shock and
cardiac/respiratory arrest.
With IV administration, give very slowly, not exceeding 1 mg per minute, with
physician present. Pain and swelling may occur at IM injection site. Efficacy of treatment
with vitamin K1 is decreased in patients with liver disease. The risk of childhood cancer is not
increased by IM administration of vitamin K1.
Black Box Warning
Warning - Hypersensitivity Reactions with Intravenous and Intramuscular use [1]

Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and
immediately after intravenous and intramuscular injection of phytonadione. Reactions
have occurred despite dilution to avoid rapid intravenous infusion and upon first dose.
Avoid the intravenous and intramuscular routes of administration unless the
subcutaneous route is not feasible and the serious risk is justified.
776
D5W, D10W, and NS.
Amikacin, ampicillin, chloramphenicol, cimetidine, epinephrine, famotidine, heparin,

hydrocortisone succinate, netilmicin, potassium chloride, ranitidine, and sodium bicarbonate.
Dobutamine and phenytoin.
Monitoring
Check prothrombin time when treating clotting abnormalities. A minimum of 2 to 4 hours is

needed for measurable improvement.
Pharmacology
Vitamin K1 (phytonadione) promotes formation of the following clotting factors in the liver:
active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component
(factor IX), and Stuart factor (factor X). Vitamin K1 does not counteract the anticoagulant
action of heparin [15].
ABOUT
Injection: Available as a 2 mg/mL aqueous dispersion in 0.5-mL ampules and 10 mg/mL

aqueous dispersion in 1-mL ampules and 2.5- and 5-mL vials. Contains 0.9% (9 mg/mL)
benzyl alcohol as a preservative. Protect from light.[15]
Oral: Oral formulation available as tablets containing 5 mg of phytonadione and in various
strengths in multivitamin products (eg, ADEKs® drops and tablets).
Protect all phytonadione products from light and store at room temperature, 25 degrees C
(77 degrees F) [16].
Extemporaneous oral solution*** Efficacy associated with the use of these
777
preparations orally is uncertain. ***
Phytonadione 1 mg/mL solution (60 mL):[17]

Add 20 mL of sterile water for injection to an amber glass bottle.
Withdraw 6 mL of phytonadione 10 mg/mL emulsion using a filter straw (5 micron) and
add to the amber bottle.
Add enough sterile water for injection to reach a final volume of 60 mL.
Amber glass bottle: When refrigerated (3.7 to 4.4 degrees C), the solution was stable
for 105 days.
Amber plastic syringe as unit doses: When refrigerated (3.7 to 4.4 degrees C), the
solution was stable for 14 days

Mix 100 mg of phytonadione with 2 grams of Cremphor EL.
Blend 50 mL of methylcellulose 1% solution with the phytonadione and Cremphor
mixture.
Add enough simple syrup to the mixture to reach a final volume of 100 mL.
Package in a light-resistant container.
Label with "Keep out of reach of children", "Use only as directed", and "Shake well"

Mix 0.1 grams of phytonadione with 2 grams of cremophor EL
Gradually add water for injection to make a clear solution then add sufficient quantity of
water for injection for a final volume of 100 mL.
To displace the oxygen, sparge nitrogen through the solution for 3 minutes.
Filter (0.2 micro pore size, 50 mm diameter membrane) the solution.
Sterilize oral syringes and end-cap seals by gamma irradiation.
Aseptically fill 1 mL amber polypropylene oral syringes with the solution.
When stored between 4 and 6 degrees C, the solution is stable for up to 6 months
778
Zidovudine
Dose
HIV Perinatal Prophylaxis

Oral
35 weeks gestation or longer: Initial, 4 mg/kg/dose orally every 12 hours [1].
Alternative weight band dose (birth to 4 weeks of age): 10 mg oral syrup (10 mg/mL) every
12 hours for 2 to less than 3 kg; 15 mg orally every 12 hours for 3 to less than 4 kg; and 20
mg orally every 12 hours for 4 to less than 5 kg [1].
30 weeks to less than 35 weeks gestation at birth: Initial, 2 mg/kg/dose orally every
12 hours (birth to 2 weeks postnatal age (PNA)), then 3 mg/kg/dose every 12 hours (2
weeks up to 4 to 6 weeks PNA) [1].
Less than 30 weeks gestation at birth: 2 mg/kg/dose orally every 12 hours (birth to 4 to
6 weeks postnatal age (PNA)) [1].
Intravenous (unable to tolerate oral)

35 weeks gestation or older: 3 mg/kg/dose IV every 12 hours [1].
30 to less than 35 weeks gestation: 1.5 mg/kg/dose IV every 12 hours (birth to 2 weeks
postnatal age (PNA)), then 2.25 mg/kg IV every 12 hours (2 weeks up to 4 to 6 weeks PNA)
[1].
Less than 30 weeks gestation: 1.5 mg/kg/dose IV every 12 hours (birth to 4 to 6 weeks
postnatal age (PNA)) [1].
HIV Treatment or Empiric Therapy

Oral
35 weeks gestation or longer: Initial, 4 mg/kg/dose orally every 12 hours (birth to 4
weeks postnatal age) [1]
Alternative weight band dose (birth to 4 weeks of age): 10 mg orally of the syrup (10
mg/mL) every 12 hours for 2 to less than 3 kg; 15 mg orally every 12 hours for 3 to less than
4 kg; and 20 mg orally every 12 hours for 4 to less than 5 kg [1].
12 mg/kg/dose orally twice daily (older than 4 weeks postnatal age) [1].
30 weeks to less than 35 weeks gestation: Initial, 2 mg/kg/dose orally every 12 hours
(birth to 2 weeks postnatal age (PNA)), then 3 mg/kg/dose every 12 hours (2 weeks up to 6
to 8 weeks PNA), then 12 mg/kg orally every 12 hours (older than 6 weeks to 8 weeks PNA)
[1].
Less than 30 weeks gestation: Initial, 2 mg/kg/dose orally every 12 hours (birth to 4
weeks postnatal age (PNA)), then 3 mg/kg/dose every 12 hours (4 weeks up to 8 to 10
weeks PNA), then 12 mg/kg orally every 12 hours (older than 8 weeks to 10 weeks PNA) [1].
Intravenous (unable to tolerate oral)

35 weeks gestation or older: 3 mg/kg/dose IV every 12 hours (birth to 4 weeks postnatal
age), then 9 mg/kg/dose orally twice daily (older than 4 weeks postnatal age) [1].
30 to less than 35 weeks gestation: 1.5 mg/kg/dose IV every 12 hours (birth to 2 weeks
postnatal age (PNA)), then 2.25 mg/kg IV every 12 hours (2 weeks up to 6 to 8 weeks PNA),
then 9 mg/kg/dose IV every 12 hours (older than 6 to 8 weeks PNA) [1].
Less than 30 weeks gestation: 1.5 mg/kg/dose IV every 12 hours (birth to 4 weeks
postnatal age (PNA)), then 2.25 mg/kg/dose IV every 12 hours (4 weeks up to 8 to 10 weeks
https://www.micromedexsolutions.com/micromedex2/librarian/CS/A7C3EC/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSY… 1/7
779
PNA), then 9 mg/kg/dose IV every 12 hours (older than 8 to 10 weeks PNA) [1].
Manufacturer recommends the total daily dose divided every 6 hours for perinatal IV
transmission prophylaxis and every 8 or 12 hours for HIV treatment and does not take into
consideration the gestational age in their dose recommendations [2].
Uses
Risk of HIV
in Newborn
Low risk of
transmission
to the regimen
Higher risk
of
transmission
breastfeeding #
Confirmed
raltegravir)
KEY
delivery.
Prevention of maternal-fetal HIV transmission .

In a phase III randomized trial (n=1684), the combination of 6 weeks of zidovudine plus 3
doses of nevirapine or the combination of 6 weeks of zidovudine plus nelfinavir and
lamiVUDine for 2 weeks was associated with a lower intrapartum transmission rate when
780
compared with zidovudine alone in infants born to women who received no antenatal
antiretroviral therapy (2.2% versus 2.5% versus 4.9%, respectively). The
zidovudine/nelfinavir/lamiVUDine regimen was associated with increased toxicity (eg,
neutropenia) [6].
Administration
Oral:
•Can be given without regard to food [2].
•Measure syrup with an appropriate-sized syringe with 0.1-mL graduation to ensure accuracy
[3].
Intravenous:
•Administer IV at a constant rate over 1 hour at a concentration not greater than 4
mg/mL.
•Rapid infusion or bolus injection should be avoided.
• Should not be given intramuscularly[2].
•Recommended concentration for IV administration is 4 mg/mL [4].
single gloves by anyone handling intact capsules or administering from a unit-dose package
[5].
In the preparation of capsules, NIOSH recommends the use of double gloves and a
protective gown. Prepare in a ventilated control device, if possible. Use respiratory protection
if not prepared in a control device. During administration, wear single gloves, and wear
eye/face protection if the formulation is hard to swallow or if the patient may resist, vomit, or
spit up [5].
In the preparation and administration of injections, NIOSH recommends the use of double
gloves and a protective gown. Prepare in a biological safety cabinet or a compounding
aseptic containment isolator; eye/face and respiratory protection may be needed. Prepare
compounds in a closed system drug transfer device. During administration, if there is a
potential that the substance could splash or if the patient may resist, use eye/face protection.
Administer certain dosage forms via a closed system drug transfer device [5].
MEDICATION SAFETY
PRECAUTIONS
Coinfection (HIV-1 and hepatitis C virus): Hepatic decompensation, some cases fatal,
has been reported in patients receiving combination antiretroviral therapy and interferon alfa
with or without ribavirin; monitoring recommended; discontinuation of zidovudine or dose
reduction or discontinuation of interferon alfa or ribavirin may be required [8].
Concomitant Use: Avoid concomitant use with doxorubicin or stavudine [8].
781
Concomitant Use: Concomitant use with ribavirin is not recommended [8].
Endocrine and metabolic: Lactic acidosis, including fatal cases, has been reported with
nucleoside analog use, including zidovudine; most cases occurred in women and risk factors
include female sex and obesity; suspend treatment if suspected [9]
Endocrine and metabolic: Lipoatrophy has been reported and is most evident in the face,
limbs, and buttocks; monitoring recommended and use of alternative treatment regimens
may be warranted [9].
Hematologic: Hematologic toxicity, including reports of neutropenia, severe anemia, and
pancytopenia have occurred; increased risk with dose and duration of therapy and especially
in patients with advanced HIV disease; monitoring recommended; dose adjustments,
interruption, discontinuation and/or blood transfusions may be necessary[8]
Hematologic: Bone marrow compromise (granulocyte count less than 1000 cells/mm(3) or
hemoglobin less than 9.5 g/dL) is associated with an increased risk for hematologic toxicities;
monitoring recommended; dose adjustments or discontinuation may be necessary [8].
Hepatic: Hepatic impairment; increased risk for hematologic toxicities; monitoring
recommended [8].
Hepatic: Severe hepatomegaly with steatosis, including fatal cases, have been reported with
nucleoside analog use, including zidovudine; most cases occurred in women and risk factors
include female sex and obesity; suspend treatment if suspected; use with caution in patients
with known risk factors for liver disease [9].
Immunologic: Autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré
syndrome) have been reported in the setting of immune reconstitution syndrome; onset is
variable and may occur several months after treatment initiation [8].
Immunologic: Immune reconstitution syndrome has been reported; patients may develop
inflammatory response to residual opportunistic infections during initial antiretroviral
treatment phase; further evaluation and treatment may be necessary [8].
Latex Allergy: Zidovudine injection vial stopper contains dry natural rubber latex (a latex
derivative) which could cause hypersensitivity reaction in latex-allergic patients [9].
Musculoskeletal: Symptomatic myopathy and myositis has been associated with prolonged
use of zidovudine [8].
Renal: Dose reduction recommended in patients with severe renal impairment (CrCl less
than 15 mL/min)[8].
Adverse Effects
Anemia and neutropenia occur frequently, and are associated with serum concentrations
greater than 3 micromol/L [10]. Mild cases usually respond to a reduction in dose . Severe
cases may require cessation of treatment and/or transfusion. Bone marrow toxicity may be
increased by concomitant administration of acyclovir, ganciclovir, and
sulfamethoxazole/trimethoprim. Transient lactic acidemia is common in infants exposed to in
utero highly active antiretroviral therapy or neonatal zidovudine [11]. Concomitant treatment
with fluconazole or methadone significantly reduces zidovudine metabolism - dosing interval
should be prolonged.
Black Box Warning
Zidovudine has been associated with hematologic toxicity, including neutropenia and severe
anemia, particularly in patients with advanced HIV disease. Prolonged use of zidovudine has
782
been associated with symptomatic myopathy. Lactic acidosis and severe hepatomegaly with
steatosis, including fatal cases, have been reported. Suspend treatment if clinical or
laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [2].
D5W and NS.
Acyclovir, amikacin, amphotericin B, aztreonam, cefepime, ceftazidime, ceftriaxone,

cimetidine, clindamycin, dexamethasone, dobutamine, dopamine, erythromycin lactobionate,
fluconazole, gentamicin, heparin, imipenem, linezolid, lorazepam, metoclopramide, morphine,
nafcillin, oxacillin, piperacillin, piperacillin-tazobactam, potassium chloride, ranitidine,
remifentanil, tobramycin, trimethoprim-sulfamethoxazole, and vancomycin.
Meropenem.
Monitoring
Prevention of maternal-fetal HIV transmission

Initial Neonatal Management: Obtain a baseline CBC with differential; timing of followup
monitoring depends on numerous exposure risks. Recheck hemoglobin and neutrophil counts
4 weeks after initiation of prophylaxis for infants who receive combination
zidovudine/lamiVUDine-containing antiretroviral prophylaxis regimens [7].
Treatment of HIV infection

[1]
1 to 2 2 to 4
†
Adverse
X X X X X
Effects ††
Adherence
††
783
CBC with X X X X
differential
¶
Chemistries
X X X X
‡¶
Random
Plasma X X
Glucose
Urinalysis X X♦
CD4 count
X X¶ X
†† ♦♦
HIV RNA
X X X X
††
Resistance
X ¶¶ X
Testing
Hepatitis B
screening X X
≈
Pharmacology
Mechanism of action: Zidovudine is a nucleoside analog that inhibits HIV replication by

interfering with viral reverse transcriptase. It is converted intracellularly in several steps to a
triphosphate derivative, metabolized via hepatic glucuronidation, then renally excreted [2].
Protein binding is approximately 25%. Zidovudine distributes into cells by passive diffusion
and is relatively lipophilic. The CSF: plasma ratio is 0.24. The relationship between serum
concentration and clinical efficacy is unclear. The oral syrup is well-absorbed, but only 65%
784
bioavailable due to significant first-pass metabolism. The serum half-life in term newborns is
3 hours, declining to 2 hours after 2 weeks of age. In preterm infants less than 33 weeks
gestation, half-life during the first two weeks of life ranges from 5 to 10 hours, decreasing to
2 to 6 hours afterward [10][12].
ABOUT
Available: Oral syrup 10 mg/mL [2].
The IV form is supplied in a concentration of 10 mg/mL in a 20 mL single-use vial. Dilute in

D5W before IV administration to a concentration not exceeding 4 mg/mL. A
dilution of 4 mg/mL may be prepared by adding 4 mL of the 10-mg/mL concentration to 6
mL D5W. After dilution, the drug is stable for 24 hours at room temperature or 48 hours if
refrigerated. Protect from light [2].
Zidovudine injection vial stopper contains dry natural rubber latex (a latex derivative) which
could cause hypersensitivity reaction in latex-allergic patients[9]

Neofax 2020 (430-791)

Uploaded by

Copyright:

Available Formats

Neofax 2020 (430-791)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Neofax 2020 (430-791)

Uploaded by

Copyright:

Available Formats

5/7/2020 NeoFax® Drug Monograph Summary - MICROMEDEX

D5W, and D10W, and NS.

Terminal Injection Site Compatibility

Terminal Injection Site Incompatibility

Butorphanol tartrate, cefoperazone, cefoxitin, ceftobiprole medocaril, chlorpromazine

Available: Regular human insulin [rDNA origin] is available as a 100-unit/mL concentration

© Copyright IBM Corporation 2020

Administer every 6 to 8 hours as a metered dose inhaler (MDI) or nebulized solution.

Anticholinergic bronchodilator for primary treatment of chronic obstructive pulmonary

Assess degree of bronchospasm.

Metered-dose inhaler: Atrovent® HFA is available in a pressurized metered-dose aerosol

© Copyright IBM Corporation 2020

0.4 to 1 mg/kg (400 to 1000 mcg/kg) per day IV continuous infusion .

Black Box Warning

Anaphylactic-type reactions, including fatalities, have followed parenteral administration.

Available as a 50 mg/mL concentration in 2-mL single-dose vials. Store at room temperature.

© Copyright IBM Corporation 2020

0.05 to 0.5 mcg/kg/minute continuous IV infusion.

Solution Preparation Calculations

Maximum concentration 20 mcg/mL. Concentrations as low as 2 mcg/mL has been used

Example (for Isoproterenol): Mix 50 mL of 10 mcg/mL solution using isoproterenol

Isoproterenol Titration Chart

D5W, D10W, and NS.

Terminal Injection Site Compatibility

Amiodarone, caffeine citrate, calcium chloride, calcium gluceptate, cimetidine, dobutamine,

Terminal Injection Site Incompatibility

Furosemide and sodium bicarbonate.

β-receptor stimulant, sympathomimetic. Increases cardiac output by 1) increasing rate

Supplied as 0.2 mg/mL solution in 1-mL and 5-mL ampuls.

© Copyright IBM Corporation 2020

Screen for Hepatitis B virus prior to initiating therapy [1].

Antiretroviral Management in the Newborn[1]

Prevention of maternal-fetal HIV transmission: In a phase III randomized trial

Pediatric FDA Approved Indications

Can be given without regard to meals [2].

Black Box Warning

Available as an oral solution in concentrations of 5 mg/mL (Epivir-HBV®) and 10 mg/mL

© Copyright IBM Corporation 2020

0.73 to 1.66 mg/kg/dose orally once daily.

The contents of a capsule can be mixed in 40 mL of apple juice and administered by NG

Observe for symptomatic improvement within 3 days. Consider intraesophageal pH

Lansoprazole inhibits gastric acid secretion by inhibition of hydrogen-potassium ATPase, the

Prevacid® is supplied as a delayed-release capsule and a delayed-release orally

© Copyright IBM Corporation 2020

Pediatric FDA Approved Indications

Intravenous (as an alternative when oral administration is not feasible)

Intravenous: Dilute to a concentration of 5 to 15 mg/mL and infuse over 15 minutes [5]. A

Immunologic: An anaphylactic reaction (erythematous rash, urticaria, hypotension)

NS, LR, and D5W.

Terminal Injection Site Compatibility

Diazepam, LORazepam, and valproate sodium.

In one small observational study (n=38) levETIRAcetam concentrations were 12.5 to 55

Mechanism of action: The exact mechanism of action is unknown [4].

Extemporaneous Suspension 50 mg/mL

© Copyright IBM Corporation 2020

Pediatric FDA Approved Indications

Black Box Warning

Mechanism of action: Tissue deiodination converts T4 to T3, the active metabolite.

Bioavailability of oral levothyroxine is approximately 40% to 80%. Absorption increased in